MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Experimental Diabetes Research' source. Sun, 21 Mar 2010 15:01:43 +0100 http://www.medworm.com/index.php?rid=3233196&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F431980.html In this study we explored the role of NEP in neuropathy related to either insulin-deficient diabetes or diet-induced obesity using NEP deficient (−/−) mice. Initial studies showed that streptozotocin, in the absence of subsequent hyperglycemia, did not induce nerve conduction slowing or paw thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP −/− mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP −/− mice exposed to either streptozotocin-induced diabetes or a high fat diet. These studies suggest that streptozotocin does not induce neurotoxicity in mice and that NEP plays a role in regulating nerve function in... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3233196 Wed, 03 Feb 2010 14:23:29 +0100 3233196 http://www.medworm.com/index.php?rid=3173540&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F827943.html This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23∘C) or cold environment (10∘C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P=.03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P=.017), decreased skin nerve fiber density (P=.037), and increased skin nitrotyrosine levels (P=.047). Cold exposure appears to hasten the develop... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3173540 Fri, 15 Jan 2010 14:11:02 +0100 3173540 http://www.medworm.com/index.php?rid=3143932&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F267107.html Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes. Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP) thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I. The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP. Of the 1040 compounds tested, 14 were considered active by virtue of their ability to ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3143932 Wed, 06 Jan 2010 14:10:59 +0100 3143932 http://www.medworm.com/index.php?rid=3123802&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F278762.html To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic β-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide). Total internal reflection fluorescent (TIRF) microscopy revealed that secondary stimulation with glimepiride, but not glucose and mitiglinide, failed to evoke fusions of insulin granules although primary stimulation with glucose, glimepiride, and mitiglinide induced equivalent numbers of exocytotic responses. Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca2+]i elevations and reductions of docked insulin granules on the plasma membrane. Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose. (Source: Experimen... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3123802 Mon, 28 Dec 2009 14:09:48 +0100 3123802 http://www.medworm.com/index.php?rid=3109260&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F605139.html The purpose of our study was to investigate whether the Trp64Arg polymorphism in β3-AR gene and the −3826A/G polymorphism in the UCP1 gene were associated with the reduction in energy expenditure and fat oxidation both in resting and aerobic exercise in Japanese. Eighty-six nonobese young healthy Japanese were recruited. Energy expenditure was measured using indirect calorimetry. The subjects performed an aerobic exercise program at 60% of their maximal heart rate for 30 minutes. The level of fat oxidation at rest and aerobic exercise of the male subjects with Trp/Arg of the β3-AR gene was significantly lower than that of the Trp/Trp genotype. No difference in FO0-30 was observed in the female subjects. There was no association between UCP-1 polymorphism and energy... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3109260 Tue, 22 Dec 2009 14:10:21 +0100 3109260 http://www.medworm.com/index.php?rid=3027970&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F107496.html (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3027970 Thu, 26 Nov 2009 14:16:27 +0100 3027970 http://www.medworm.com/index.php?rid=3017822&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F737686.html Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=3017822 Mon, 23 Nov 2009 14:05:41 +0100 3017822 http://www.medworm.com/index.php?rid=2956316&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F136501.html Conclusions. There is a high prevalence of metabolic syndrome in this urban population of the northern west of Iran. Focus of cardiovascular prevention should be undertaken in this area. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2956316 Wed, 04 Nov 2009 14:17:38 +0100 2956316 http://www.medworm.com/index.php?rid=2936439&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F631026.html Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN-α), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2′,5′-oligoadenylate synthetase (2′5′AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN-α and/or poly(I:C) (a synthetic dsRNA). Results showed that, following IFN-α stimulation, increases in 2′5′AS levels and activities were significantly higher in beta than alpha cells (P<.001), whereas increases in PKR level and activity were comparable in the tw... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2936439 Thu, 29 Oct 2009 14:11:31 +0100 2936439 http://www.medworm.com/index.php?rid=2906272&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F363787.html Conclusion. Overt diabetes alters cyclosporine disposition by modulating its clearance. Abnormalities in the lipid profile, among other factors, may contribute to the accelerated metabolic degradation of cyclosporine under hyperglycemic conditions. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2906272 Tue, 20 Oct 2009 13:11:20 +0100 2906272 http://www.medworm.com/index.php?rid=2881859&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F793281.html We investigated mechanisms underlying progressive axonal dysfunction and structural deficits in type 1 BB/Wor-rats from 1 week to 10 month diabetes duration. Motor and sensory conduction velocities were decreased after 4 and 6 weeks of diabetes and declined further over the remaining 9 months. Myelinated sural nerve fibers showed progressive deficits in fiber numbers and sizes. Structural deficits in unmyelinated axonal size were evident at 2 month and deficits in number were present at 4 mo. These changes were preceded by decreased availability of insulin, C-peptide and IGF-1 and decreased expression of neurofilaments and β-III-tubulin. Upregulation of phosphorylating stress kinases like Cdk5, p-GSK-3β, and p42/44 resulted in increa... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2881859 Mon, 12 Oct 2009 13:07:07 +0100 2881859 http://www.medworm.com/index.php?rid=2848357&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F329632.html Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swo... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2848357 Thu, 01 Oct 2009 16:36:29 +0100 2848357 http://www.medworm.com/index.php?rid=2749066&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F291027.html In conclusion, the strong positive relation of PTHrP with glucose in the fasting state in patients with type 2 diabetes mellitus raises several questions for further experimentation concerning its exact role and physiological significance. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2749066 Tue, 01 Sep 2009 12:05:20 +0100 2749066 http://www.medworm.com/index.php?rid=2710429&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F715057.html In this study, SDT fatty rats were subjected to pair-feeding with SDT-+/+ (SDT) rats from 6 to 22 weeks of age. The ratio of visceral fat weight to subcutaneous fat weight (V/S) decreased at 12 weeks of age in the pair-feeding rats. The intraperitoneal fat weight such as epididymal and retroperitoneal fat weight decreased, whereas mesenteric fat weight had no change. Cell size of the epididymal fat in the pair-feeding rats tended to decrease. Glucose oxidation level in epididymal fat in the pair-feeding rats at 12 weeks of age was recovered to a similar level with that in SDT rats. These results indicated that SDT fatty rat is a useful model to evaluate the functional or the morphological features in adipose tissue and develop a novel drug for antiobesity. (Source: Experimental Diabetes Re... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2710429 Wed, 19 Aug 2009 10:22:15 +0100 2710429 http://www.medworm.com/index.php?rid=2574359&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F910783.html Peroxisome proliferator-activated receptor (PPARγ), a ligand-dependent transcription factor, negatively modulates high glucose effects. We postulated that rosiglitazone (RSG), an activator of PPARγ prevents the upregulation of vascular endothelial growth factor (VEGF) and collagen IV by mesangial cells exposed to high glucose. Primary cultured rat mesangial cells were growth-arrested in 5.6 mM (NG) or 25 mM D-glucose (HG) for up to 48 hours. In HG, PPARγ mRNA and protein were reduced within 3 h, and enhanced ROS generation, expression of p22phox, VEGF and collagen IV, and PKC-ζ membrane association were prevented by RSG. In NG, inhibition of PPARγ caused ROS generation and VEGF expression that were unchanged by RSG. Reduced AMP... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2574359 Tue, 07 Jul 2009 10:53:45 +0100 2574359 http://www.medworm.com/index.php?rid=2572256&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F429593.html Conclusion. Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2572256 Mon, 06 Jul 2009 10:51:56 +0100 2572256 http://www.medworm.com/index.php?rid=2465309&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F819123.html Patients with fulminant type 1 diabetes almost completely lack C-peptide even soon after the onset of the disease, and the deficiency continues for the rest of their life. Thus, fulminant type 1 diabetes could serve as a good model of nature to explore the physiological role of C-peptide. For example, patients with fulminant type 1 diabetes have diabetic chronic complications more frequently than those with classical autoimmune type 1 diabetes 5 years after the onset of diabetes, and the higher prevalence could be partly attributable to the complete lack of C-peptide in fulminant type 1 diabetes. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465309 Tue, 09 Jun 2009 16:47:22 +0100 2465309 http://www.medworm.com/index.php?rid=2465308&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F230458.html Diabetic polyneuropathy (DPN) occurs more frequently in type 1 diabetes resulting in a more severe DPN. The differences in DPN between the two types of diabetes are due to differences in the availability of insulin and C-peptide. Insulin and C-peptide provide gene regulatory effects on neurotrophic factors with effects on axonal cytoskeletal proteins and nerve fiber integrity. A significant abnormality in type 1 DPN is nodal degeneration. In the type 1 BB/Wor-rat, C-peptide replacement corrects metabolic abnormalities ameliorating the acute nerve conduction defect. It corrects abnormalities of neurotrophic factors and the expression of neuroskeletal proteins with improvements of axonal size and function. C-peptide corrects the expression of nodal adhesive molecules with prevention and repa... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465308 Tue, 09 Jun 2009 16:47:22 +0100 2465308 http://www.medworm.com/index.php?rid=2465307&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F371716.html An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies sh... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465307 Tue, 09 Jun 2009 16:47:22 +0100 2465307 http://www.medworm.com/index.php?rid=2465306&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F421287.html The presence of fibrillar protein deposits (amyloid) of human islet amyloid polypeptide (hIAPP) in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet β-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-induced β-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of β-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer_s disease, Parkinson's disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465306 Tue, 09 Jun 2009 16:47:22 +0100 2465306 http://www.medworm.com/index.php?rid=2465305&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F730594.html Conclusion/interpretation. C-peptide and its C-terminal fragments are equally effective in improving erythrocyte deformability in type 1 diabetes. The C-terminal residues of C-peptide are causally involved in this effect. The signal transduction pathway is Ca2+-dependent and involves activation of red blood cell Na+,K+-ATPase. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465305 Tue, 09 Jun 2009 16:47:22 +0100 2465305 http://www.medworm.com/index.php?rid=2465304&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F697035.html In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465304 Tue, 09 Jun 2009 16:47:22 +0100 2465304 http://www.medworm.com/index.php?rid=2465303&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F576862.html Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its b... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465303 Tue, 09 Jun 2009 16:47:22 +0100 2465303 http://www.medworm.com/index.php?rid=2465302&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F281536.html The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studi... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465302 Tue, 09 Jun 2009 16:47:22 +0100 2465302 http://www.medworm.com/index.php?rid=2465301&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F738101.html The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and p38 phosphorylation to a single bout of contractile stimuli ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465301 Tue, 09 Jun 2009 16:47:22 +0100 2465301 http://www.medworm.com/index.php?rid=2465300&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F865850.html Amyloid formation is cytotoxic and can activate the caspase cascade. Here, we monitor caspase-3-like activity as reduction of fluorescence resonance energy transfer (FRET) using the contstruct pFRET2-DEVD containing enhanced cyan fluorescent protin (EYFP) linked by the caspase-3 specific cleavage site residues DEVD. Beta-TC-6 cells were transfected, and the fluoorescence was measured at 440 nm excitation and 535 nm (EYFP) and 480 nm (ECFP) emission wavelength. Cells were incubated with recombinant pro lset Amyloid Polypeptide (rec prolAPP) or the processing metabolites of prolAPP; the N-terminal flanking peptide withIAPP (recN+IAPP); IAPP with the C-terminal flanking peptied (recIAPP+C) and lslet Amyloid Polypeptide (recIAPP) . Peptides were added in solubilized from ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465300 Tue, 09 Jun 2009 16:47:22 +0100 2465300 http://www.medworm.com/index.php?rid=2465299&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F256954.html The molecular mechanism of amyloid formation by the islet amyloid polypeptide (IAPP) has been intensively studied since its identification in the late 1980s. The IAPP(20–29) region is considered to be the central amyloidogenic module of the polypeptide. This assumption is mainly based on the amyloidogenic properties of the region and on the large sequence diversity within this region between the human and mouse IAPP, as the mouse IAPP does not form amyloids. A few years ago, another region within IAPP was identified that seems to be at least as important as IAPP(20–29) in facilitation of molecular recognition that leads to amyloid formation. Here, we reinforce our and others' previous findings by analyzing supporting evidence from the recent literature. Moreover, we provide new... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465299 Tue, 09 Jun 2009 16:47:22 +0100 2465299 http://www.medworm.com/index.php?rid=2465298&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F230837.html Acute-phase serum amyloid A (A-SAA) was shown recently to correlate with obesity and insulin resistance in humans. However, the mechanisms linking obesity-associated inflammation and elevated plasma A-SAA to insulin resistance are poorly understood. Using high-fat diet- (HFD-) fed mice, we found that plasma A-SAA was increased early upon HFD feeding and was tightly associated with systemic insulin resistance. Plasma A-SAA elevation was due to induction of Saa1 and Saa2 expression in liver but not in adipose tissue. In adipose tissue Saa3 was the predominant isoform and the earliest inflammatory marker induced, suggesting it is important for initiation of adipose tissue inflammation. To assess the potential impact of A-SAA on adipose tissue insulin resistance, we treated 3T3-L1 adipocytes w... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465298 Tue, 09 Jun 2009 16:47:22 +0100 2465298 http://www.medworm.com/index.php?rid=2465297&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F304513.html This study examined α-cell function in mice with β-cell specific overexpression of human IAPP (hIAPP) after an oral protein gavage (75 mg whey protein/mouse). Baseline glucagon levels were higher in transgenic mice (41±4.0 pg/mL, n=6) than in wildtype animals (19±5.1 pg/mL, n=5, P=.015). In contrast, the glucagon response to protein was impaired in transgenic animals (21±2.7 pg/mL in transgenic mice versus 38±5.7 pg/mL in wildtype mice at 15 minutes; P=.027). Baseline insulin levels did not differ between the groups, while the insulin response, as the glucagon response, was impaired after protein challenge (P=.018). Glucose levels were not different between the groups and did not change significantly after protein... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465297 Tue, 09 Jun 2009 16:47:22 +0100 2465297 http://www.medworm.com/index.php?rid=2465296&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F165360.html In this study, we investigated whether rat beta cells can be isolated from nonbeta endocrine cells by manipulating the flavin adenine dinucleotide (FAD) and nicotinamide-adenine dinucleotide phosphate (NAD(P)H) autofluorescence. Beta cells were isolated from dispersed islets by flow cytometry, based on their high FAD and NAD(P)H fluorescence. To improve beta cell yield and purity, the cellular FAD and NAD(P)H contents were altered by preincubation in culture media containing varying amounts of D-glucose and amino acids. Manipulation of the cellular FAD and NAD(P)H fluorescence improves beta cell yield and purity after sorting. This method is also a fast and reliable method to measure beta cell functional viability. A conceivable application is assessing beta cell viability before transplan... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465296 Tue, 09 Jun 2009 16:47:22 +0100 2465296 http://www.medworm.com/index.php?rid=2465295&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F176245.html During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulating Na+K+ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin sec... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465295 Tue, 09 Jun 2009 16:47:22 +0100 2465295 http://www.medworm.com/index.php?rid=2465294&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F271958.html Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465294 Tue, 09 Jun 2009 16:47:22 +0100 2465294 http://www.medworm.com/index.php?rid=2465293&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F305403.html The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001), Cinulin increased 80% (P<.01). Kidney wet and dry weights increased 10%–12% (P<.05), and glomerular tuft area increased 9.3% (P<.001). Phlorizin prevented proteinuria, hyperfiltration, an... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465293 Tue, 09 Jun 2009 16:47:22 +0100 2465293 http://www.medworm.com/index.php?rid=2465292&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F818341.html We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet's membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long-spacing collagen fibrils were observed in Descemet's membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age-dependent increase in the density of the long-spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long-spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465292 Tue, 09 Jun 2009 16:47:22 +0100 2465292 http://www.medworm.com/index.php?rid=2465291&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F312060.html Conclusions. The combination of an exhaustive domain-based compilation of the transcriptome with gene array data of interest to the islet biologist affords novel methods for multidimensional querying between individual datasets in a rapid fashion, presently not available elsewhere. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465291 Tue, 09 Jun 2009 16:47:22 +0100 2465291 http://www.medworm.com/index.php?rid=2465290&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F384219.html (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465290 Tue, 09 Jun 2009 16:47:22 +0100 2465290 http://www.medworm.com/index.php?rid=2465289&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F429274.html Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils d... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465289 Tue, 09 Jun 2009 16:47:22 +0100 2465289 http://www.medworm.com/index.php?rid=2465288&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F638467.html We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. We selected twenty-four Wistar rats; half of them were made diabetic by intraperitoneal injection of a single 60 mg/kg dose of streptozotocin (STZ, IP), while the others received normal saline and served as controls. The expressions of Bcl-2, Bcl-xL, and Bax mRNA and proteins were measured using RT-PCR and western blotting, respectively. Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. The result showed that mRNA and protein levels of Bcl-2 and Bcl-xL were lower in hippocampus of diabetic group than that of the control group, wherea... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465288 Tue, 09 Jun 2009 16:47:22 +0100 2465288 http://www.medworm.com/index.php?rid=2465287&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F704045.html Conclusion. Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465287 Tue, 09 Jun 2009 16:47:22 +0100 2465287 http://www.medworm.com/index.php?rid=2465286&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F728763.html We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2, Wnt2b, β-catenin, pGSK3β, TCF3, cyclinD1, and c-myc, were undetectable or expressed at low levels in islets from nondiabetic individuals, but were also upregulated specifically in islets of type II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt activation in that setting was due to soluble Wnt factors. These data support a model in which the Wnt pathway plays a dynamic role in the pathogenesis of type II diabetes and suggest manipulation of Wnt signaling as a new approac... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465286 Tue, 09 Jun 2009 16:47:22 +0100 2465286 http://www.medworm.com/index.php?rid=2465285&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F562985.html Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphas... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465285 Tue, 09 Jun 2009 16:47:22 +0100 2465285 http://www.medworm.com/index.php?rid=2465284&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F897508.html Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465284 Tue, 09 Jun 2009 16:47:22 +0100 2465284 http://www.medworm.com/index.php?rid=2465283&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2008%2F528354.html (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465283 Tue, 09 Jun 2009 16:47:22 +0100 2465283 http://www.medworm.com/index.php?rid=2465282&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F696378.html Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465282 Tue, 09 Jun 2009 16:47:22 +0100 2465282 http://www.medworm.com/index.php?rid=2465281&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F835650.html Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24. Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.lyp/lyp rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.+/+ rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.lyp/lyp rat. Gimap4 and Gimap1 each had one amino acid substituti... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465281 Tue, 09 Jun 2009 16:47:22 +0100 2465281 http://www.medworm.com/index.php?rid=2465280&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fedr%2F2009%2F912327.html The purpose of this study was to determine whether AVE7688 a drug that inhibits both angiotensin converting enzyme and neutral endopeptidase activity protects vascular and nerve functions in an animal model of metabolic syndrome. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with AVE7688. Vasodilation in epineurial arterioles was measured by videomicroscopy and nerve conduction velocity was measured following electrical stimulation. Treatment with AVE7688 improved vascular relaxation in response to acetylcholine and motor and sensory nerve conduction velocity. In obese Zucker rats superoxide levels and nitrotyrosine staining were elevated in the aorta and treatment corrected both conditions. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and demonstra... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2465280 Tue, 09 Jun 2009 16:47:22 +0100 2465280 http://www.medworm.com/index.php?rid=2459932&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F912327 The purpose of this study was to determine whether AVE7688 a drug that inhibits both angiotensin converting enzyme and neutral endopeptidase activity protects vascular and nerve functions in an animal model of metabolic syndrome. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with AVE7688. Vasodilation in epineurial arterioles was measured by videomicroscopy and nerve conduction velocity was measured following electrical stimulation. Treatment with AVE7688 improved vascular relaxation in response to acetylcholine and motor and sensory nerve conduction velocity. In obese Zucker rats superoxide levels and nitrotyrosine staining were elevated in the aorta and treatment corrected both conditions. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and demonstra... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2459932 Sun, 07 Jun 2009 19:11:22 +0100 2459932 http://www.medworm.com/index.php?rid=2383914&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F835650 Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24. Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.lyp/lyp rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.+/+ rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.lyp/lyp rat. Gimap4 and Gimap1 each had one amino acid substituti... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2383914 Sun, 03 May 2009 20:05:46 +0100 2383914 http://www.medworm.com/index.php?rid=2333326&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F696378 Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2333326 Sat, 18 Apr 2009 03:51:54 +0100 2333326 http://www.medworm.com/index.php?rid=2308183&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F528354 (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2308183 Tue, 07 Apr 2009 19:50:55 +0100 2308183 http://www.medworm.com/index.php?rid=2269601&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F897508 Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2269601 Tue, 17 Mar 2009 08:32:06 +0100 2269601 http://www.medworm.com/index.php?rid=2242079&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F562985 Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphas... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2242079 Sat, 07 Mar 2009 14:53:20 +0100 2242079 http://www.medworm.com/index.php?rid=2116788&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F728763 We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2, Wnt2b, β-catenin, pGSK3β, TCF3, cyclinD1, and c-myc, were undetectable or expressed at low levels in islets from nondiabetic individuals, but were also upregulated specifically in islets of type II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt activation in that setting was due to soluble Wnt factors. These data support a model in which the Wnt pathway plays a dynamic role in the pathogenesis of type II diabetes and suggest manipulation of Wnt signaling as a new approac... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2116788 Wed, 21 Jan 2009 07:08:39 +0100 2116788 http://www.medworm.com/index.php?rid=2078388&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F704045 Conclusion. Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=2078388 Sun, 04 Jan 2009 13:22:06 +0100 2078388 http://www.medworm.com/index.php?rid=1871389&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F638467 We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. We selected twenty-four Wistar rats; half of them were made diabetic by intraperitoneal injection of a single 60 mg/kg dose of streptozotocin (STZ, IP), while the others received normal saline and served as controls. The expressions of Bcl-2, Bcl-xL, and Bax mRNA and proteins were measured using RT-PCR and western blotting, respectively. Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. The result showed that mRNA and protein levels of Bcl-2 and Bcl-xL were lower in hippocampus of diabetic group than that of the control group, wherea... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1871389 Mon, 13 Oct 2008 14:47:55 +0100 1871389 http://www.medworm.com/index.php?rid=1826936&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F429274 Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils d... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1826936 Thu, 25 Sep 2008 18:13:50 +0100 1826936 http://www.medworm.com/index.php?rid=1803335&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F384219 (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1803335 Thu, 18 Sep 2008 15:02:19 +0100 1803335 http://www.medworm.com/index.php?rid=1776192&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F312060 Conclusions. The combination of an exhaustive domain-based compilation of the transcriptome with gene array data of interest to the islet biologist affords novel methods for multidimensional querying between individual datasets in a rapid fashion, presently not available elsewhere. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1776192 Tue, 09 Sep 2008 14:39:30 +0100 1776192 http://www.medworm.com/index.php?rid=1750834&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F818341 We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet's membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long-spacing collagen fibrils were observed in Descemet's membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age-dependent increase in the density of the long-spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long-spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1750834 Tue, 02 Sep 2008 13:51:28 +0100 1750834 http://www.medworm.com/index.php?rid=1734737&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F305403 The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001), Cinulin increased 80% (P<.01). Kidney wet and dry weights increased 10%–12% (P<.05), and glomerular tuft area increased 9.3% (P<.001). Phlorizin prevented proteinuria, hyperfiltration, an... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1734737 Wed, 27 Aug 2008 14:28:41 +0100 1734737 http://www.medworm.com/index.php?rid=1658344&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F271958 Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1658344 Mon, 28 Jul 2008 12:43:50 +0100 1658344 http://www.medworm.com/index.php?rid=1658343&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F176245 During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulating Na+K+ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin sec... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1658343 Mon, 28 Jul 2008 12:43:50 +0100 1658343 http://www.medworm.com/index.php?rid=1658342&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F165360 In this study, we investigated whether rat beta cells can be isolated from nonbeta endocrine cells by manipulating the flavin adenine dinucleotide (FAD) and nicotinamide-adenine dinucleotide phosphate (NAD(P)H) autofluorescence. Beta cells were isolated from dispersed islets by flow cytometry, based on their high FAD and NAD(P)H fluorescence. To improve beta cell yield and purity, the cellular FAD and NAD(P)H contents were altered by preincubation in culture media containing varying amounts of D-glucose and amino acids. Manipulation of the cellular FAD and NAD(P)H fluorescence improves beta cell yield and purity after sorting. This method is also a fast and reliable method to measure beta cell functional viability. A conceivable application is assessing beta cell viability before transplan... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1658342 Mon, 28 Jul 2008 12:43:50 +0100 1658342 http://www.medworm.com/index.php?rid=1583190&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F304513 This study examined α-cell function in mice with β-cell specific overexpression of human IAPP (hIAPP) after an oral protein gavage (75 mg whey protein/mouse). Baseline glucagon levels were higher in transgenic mice (41±4.0 pg/mL, n=6) than in wildtype animals (19±5.1 pg/mL, n=5, P=.015). In contrast, the glucagon response to protein was impaired in transgenic animals (21±2.7 pg/mL in transgenic mice versus 38±5.7 pg/mL in wildtype mice at 15 minutes; P=.027). Baseline insulin levels did not differ between the groups, while the insulin response, as the glucagon response, was impaired after protein challenge (P=.018). Glucose levels were not different between the groups and did not change significantly after protein... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1583190 Mon, 07 Jul 2008 11:38:07 +0100 1583190 http://www.medworm.com/index.php?rid=1536822&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F230837 Acute-phase serum amyloid A (A-SAA) was shown recently to correlate with obesity and insulin resistance in humans. However, the mechanisms linking obesity-associated inflammation and elevated plasma A-SAA to insulin resistance are poorly understood. Using high-fat diet- (HFD-) fed mice, we found that plasma A-SAA was increased early upon HFD feeding and was tightly associated with systemic insulin resistance. Plasma A-SAA elevation was due to induction of Saa1 and Saa2 expression in liver but not in adipose tissue. In adipose tissue Saa3 was the predominant isoform and the earliest inflammatory marker induced, suggesting it is important for initiation of adipose tissue inflammation. To assess the potential impact of A-SAA on adipose tissue insulin resistance, we treated 3T3-L1 adipocytes w... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1536822 Sun, 22 Jun 2008 21:59:24 +0100 1536822 http://www.medworm.com/index.php?rid=1510094&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F256954 The molecular mechanism of amyloid formation by the islet amyloid polypeptide (IAPP) has been intensively studied since its identification in the late 1980s. The IAPP(20–29) region is considered to be the central amyloidogenic module of the polypeptide. This assumption is mainly based on the amyloidogenic properties of the region and on the large sequence diversity within this region between the human and mouse IAPP, as the mouse IAPP does not form amyloids. A few years ago, another region within IAPP was identified that seems to be at least as important as IAPP(20–29) in facilitation of molecular recognition that leads to amyloid formation. Here, we reinforce our and others' previous findings by analyzing supporting evidence from the recent literature. Moreover, we provide new... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1510094 Thu, 12 Jun 2008 00:38:33 +0100 1510094 http://www.medworm.com/index.php?rid=1510093&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F865850 Amyloid formation is cytotoxic and can activate the caspase cascade. Here, we monitor caspase-3-like activity as reduction of fluorescence resonance energy transfer (FRET) using the contstruct pFRET2-DEVD containing enhanced cyan fluorescent protin (EYFP) linked by the caspase-3 specific cleavage site residues DEVD. Beta-TC-6 cells were transfected, and the fluoorescence was measured at 440 nm excitation and 535 nm (EYFP) and 480 nm (ECFP) emission wavelength. Cells were incubated with recombinant pro lset Amyloid Polypeptide (rec prolAPP) or the processing metabolites of prolAPP; the N-terminal flanking peptide withIAPP (recN+IAPP); IAPP with the C-terminal flanking peptied (recIAPP+C) and lslet Amyloid Polypeptide (recIAPP) . Peptides were added in solubilized from ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1510093 Thu, 12 Jun 2008 00:38:33 +0100 1510093 http://www.medworm.com/index.php?rid=1492683&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F738101 The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and p38 phosphorylation to a single bout of contractile stimuli ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1492683 Wed, 04 Jun 2008 17:33:04 +0100 1492683 http://www.medworm.com/index.php?rid=1489638&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1080%2F15438600303730 The authors have derived a new β-cell line (βIns2−/−lacZ) from Ins2−/− mice that carry the lacZ reporter gene under control of the Ins2 promoter. βIns2−/−lacZ cells stained positively using anti-insulin antibody, expressed β-cell–specific genes encoding the transcription factor PDX-1, glucokinase, and Glut-2, retained glucose-responsiveness for insulin secretion, and expressed the lacZ gene. Analysis of Ins1 expression by reverse transcriptase–polymerase chain reaction (RT-PCR) showed that Ins1 transcripts were significantly raised to compensate for the lack of Ins2 transcripts in βIns2−/−lacZ cells, as compared to those found in βTC1 cells expressing both Ins1/Ins2. Thus, transcriptional up-... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489638 Tue, 03 Jun 2008 22:14:09 +0100 1489638 http://www.medworm.com/index.php?rid=1489637&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1080%2F15438600303731 Insulin resistance is the primary cause of type 2 diabetes. However, if compensated by increased insulin production, insulin resistance by itself does not lead to overt disease. Type 2 diabetes develops when this compensation is insufficient, due to defects in β-cell function and in regulation of the β-cell mass. β-Cell transplantation, as well as approaches that replenish or preserve the endogenous β-cell mass, may facilitate the treatment of type 2 diabetes in patients requiring exogenous insulin. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489637 Tue, 03 Jun 2008 22:14:09 +0100 1489637 http://www.medworm.com/index.php?rid=1489636&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F72741 There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR) on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet) displayed decreased glucose/insulin (G/I) ratio and insulin sensitivity index (ISI0,120) indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489636 Tue, 03 Jun 2008 22:14:09 +0100 1489636 http://www.medworm.com/index.php?rid=1489635&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F51837 Breakdown of the inner blood-retinal barrier (iBRB) occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME) as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs) forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ) integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3) in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT) mice and in Gal-3−/− transgenic mice. Blood glucose was monitored and AGE levels we... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489635 Tue, 03 Jun 2008 22:14:09 +0100 1489635 http://www.medworm.com/index.php?rid=1489634&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F43603 Oxygen metabolism is essential for sustaining aerobic life, and normal cellular homeostasis works on a fine balance between the formation and elimination of reactive oxygen species (ROS). Oxidative stress, a cytopathic consequence of excessive production of ROS and the suppression of ROS removal by antioxidant defense system, is implicated in the development of many diseases, including Alzheimer's disease, and diabetes and its complications. Retinopathy, a debilitating microvascular complication of diabetes, is the leading cause of acquired blindness in developed countries. Many diabetes-induced metabolic abnormalities are implicated in its development, and appear to be influenced by elevated oxidative stress; however the exact mechanism of its development remains elusive. Increased su... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489634 Tue, 03 Jun 2008 22:14:09 +0100 1489634 http://www.medworm.com/index.php?rid=1489633&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F15803 This study was designed to examine the antioxidant defense by ethanolic extract of Embelia ribes on streptozotocin-(40 mg/kg, intravenously, single-injection) induced diabetes in Wistar rats. Forty days of oral feeding the extract (100 mg/kg and 200 mg/kg) to diabetic rats resulted in significant (P<.01) decrease in blood glucose, blood glycosylated haemoglobin, serum lactate dehydrogenase, creatine kinase, and increase in blood glutathione levels as compared to pathogenic diabetic rats. Further, the extract also significantly (P<.01) decreased the pancreatic thiobarbituric acid-reactive substances (TBARS) levels and significantly (P<.01) increased the superoxide dismutase, catalase, and glutathione levels as compared to above levels in pancreatic tissue of pathogenic ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489633 Tue, 03 Jun 2008 22:14:09 +0100 1489633 http://www.medworm.com/index.php?rid=1489632&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F21976 Conclusions. Peroxynitrite accumulation in the retinal microvasculature, the site of histopathology, fails to normalize after reversal of hyperglycemia, and superoxide remains inadequately scavenged. This failure of reversal of peroxynitrite accumulation could be, in part, responsible for the resistance of diabetic retinopathy to reverse after termination of PC. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489632 Tue, 03 Jun 2008 22:14:09 +0100 1489632 http://www.medworm.com/index.php?rid=1489631&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F36150 Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489631 Tue, 03 Jun 2008 22:14:09 +0100 1489631 http://www.medworm.com/index.php?rid=1489630&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F39765 Elevated glutamate is implicated in the pathology of PDR. The ability to rapidly assess the glutamate and amino acid content of vitreous provides a more complete picture of the chemical changes occurring at the diabetic retina and may lead to a better understanding of the pathology of PDR. Vitreous humor was collected following vitrectomies of patients with PDR and control conditions of macular hole or epiretinal membrane. A capillary electrophoresis method was developed to quantify glutamate and arginine. The analysis is relatively fast (<6 minutes) and utilizes a poly(ethylene)oxide and sodium dodecylsulfate run buffer. Both amino acid levels show significant increases in PDR patients versus controls and are comparable to other reports. The levels of vitreal glutamate vary inverse... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489630 Tue, 03 Jun 2008 22:14:09 +0100 1489630 http://www.medworm.com/index.php?rid=1489629&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F52487 Diabetic retinopathy remains a major cause of worldwide preventable blindness. Measures to avoid blindness include medical management (control of blood sugar, blood pressure, and serum lipids) and ocular management (laser photocoagulation and pars plana vitrectomy). Adjunctive pharmacologic therapies (intravitreal triamcinolone acetonide and anti-vascular endothelial growth factor agents) have shown early promise in the treatment of both diabetic macular edema and proliferative diabetic retinopathy. Other medications under investigation include the fluocinolone acetonide implantable device, extended-release dexamethasone implant, oral ruboxistaurin, and intravitreal hyaluronidase. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489629 Tue, 03 Jun 2008 22:14:09 +0100 1489629 http://www.medworm.com/index.php?rid=1489628&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F61038 The polyol pathway is a two-step metabolic pathway in which glucose is reduced to sorbitol, which is then converted to fructose. It is one of the most attractive candidate mechanisms to explain, at least in part, the cellular toxicity of diabetic hyperglycemia because (i) it becomes active when intracellular glucose concentrations are elevated, (ii) the two enzymes are present in human tissues and organs that are sites of diabetic complications, and (iii) the products of the pathway and the altered balance of cofactors generate the types of cellular stress that occur at the sites of diabetic complications. Inhibition (or ablation) of aldose reductase, the first and rate-limiting enzyme in the pathway, reproducibly prevents diabetic retinopathy in diabetic rodent models, but the results of ... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489628 Tue, 03 Jun 2008 22:14:09 +0100 1489628 http://www.medworm.com/index.php?rid=1489627&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F95103 Diabetes causes metabolic and physiologic abnormalities in the retina, and these changes suggest a role for inflammation in the development of diabetic retinopathy. These changes include upregulation of iNOS, COX-2, ICAM-1, caspase 1, VEGF, and NF-κB, increased production of nitric oxide, prostaglandin E2, IL-1β, and cytokines, as well as increased permeability and leukostasis. Using selective pharmacologic inhibitors or genetically modified animals, an increasing number of therapeutic approaches have been identified that significantly inhibit development of at least the early stages of diabetic retinopathy, especially occlusion and degeneration of retinal capillaries. A common feature of a number of these therapies is that they inhibit production of inflammatory mediators. T... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489627 Tue, 03 Jun 2008 22:14:09 +0100 1489627 http://www.medworm.com/index.php?rid=1489626&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F67435 The Siraitia grosvenorii polysaccharide (SGP) from the Siraitia grosvenorii (Swingle) was isolated and purified. The therapeutic effects of SGP on diabetic rabbits induced by feeding high fat/high sucrose chow were studied. After administration of SGP for 4 weeks, the fasting blood glucose (FBG), plasma insulin levels (INS), plasma total cholesterol (TC), triglyceride (TG), and HDL-C were assayed. The results showed that administration of SGP can significantly decrease plasma total cholesterol, triglyceride, and glucose levels; and increase HDL-C levels after 4 weeks of treatment. The antihyperglycaemic effect of SGP at dose of 100 mg⋅kg−1 bw was the most significant in three dosage groups. Furthermore, SGP could restore the blood lipid levels of diabetic rabbits (P&#x00... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489626 Tue, 03 Jun 2008 22:14:09 +0100 1489626 http://www.medworm.com/index.php?rid=1489625&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F31867 Dysfunction and death of microvascular cells and imbalance between the production and the degradation of extracellular matrix (ECM) proteins are a characteristic feature of diabetic retinopathy (DR). Glucose-induced biochemical alterations in the vascular endothelial cells may activate a cascade of signaling pathways leading to increased production of ECM proteins and cellular dysfunction/death. Chronic diabetes leads to the activation of a number of signaling proteins including protein kinase C, protein kinase B, and mitogen-activated protein kinases. These signaling cascades are activated in response to hyperglycemia-induced oxidative stress, polyol pathway, and advanced glycation end product formation among others. The aberrant signaling pathways ultimately lead to activation of transcr... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489625 Tue, 03 Jun 2008 22:14:09 +0100 1489625 http://www.medworm.com/index.php?rid=1489624&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F76271 High prevalence rates of type 2 diabetes are being observed in native Canadian communities. It is believed that native populations have a higher prevalence rate of vascular complications than nonnatives. The Southern Alberta Study of Diabetic Retinopathy (DR) examined the prevalence and incidence of DR and associated metabolic abnormalities in native and nonnative subjects. Prevalence rates of DR in type 2 diabetic native and nonnative subjects were identical, with a prevalence rate of 40%. Native subjects with retinopathy, however, tended to have more advanced changes of retinopathy compared to the nonnative subjects. Key factors such as A1c, blood pressure, duration of diabetes, and lipid values were not significantly different between the two cohorts. These data indicate that ethnic... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489624 Tue, 03 Jun 2008 22:14:09 +0100 1489624 http://www.medworm.com/index.php?rid=1489623&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2007%2F69527 (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489623 Tue, 03 Jun 2008 22:14:09 +0100 1489623 http://www.medworm.com/index.php?rid=1489622&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F457912 Recent results indicate that proinsulin C-peptide, contrary to previous views, exerts important physiological effects and shows the characteristics of a bioactive peptide. Studies in type 1 diabetes, involving animal models as well as patients, demonstrate that C-peptide in replacement doses has the ability to improve peripheral nerve function and prevent or reverse the development of nerve structural abnormalities. Peripheral nerve function, as evaluated by determination of sensory nerve conduction velocity and quantitative sensory testing, is improved by C-peptide replacement in diabetes type 1 patients with early stage neuropathy. Similarly, autonomic nerve dysfunction is ameliorated following administration of C peptide for up to 3 months. As evaluat... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489622 Tue, 03 Jun 2008 22:14:09 +0100 1489622 http://www.medworm.com/index.php?rid=1489621&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F672021 Conclusion. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489621 Tue, 03 Jun 2008 22:14:09 +0100 1489621 http://www.medworm.com/index.php?rid=1489620&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F635158 C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these obser... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489620 Tue, 03 Jun 2008 22:14:09 +0100 1489620 http://www.medworm.com/index.php?rid=1489619&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F769483 During the recent years, multiple studies demonstrated that C-peptide is not an inert peptide, but exerts important physiological effects. C-peptide binds to cell membranes, stimulates the Na,K-ATPase and the endothelial nitric oxide (NO) synthase. Moreover, there is evidence that C-peptide decreases glomerular hyperfiltration and increases glucose utilisation. Nevertheless, there is still limited knowledge concerning mechanisms leading to an increased glucose utilisation either in rats or in humans. The aim of this paper is to give an overview over the published studies regarding C-peptide and glucose metabolism from in vitro studies to longer lasting studies in humans. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489619 Tue, 03 Jun 2008 22:14:09 +0100 1489619 http://www.medworm.com/index.php?rid=1489618&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F385108 Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489618 Tue, 03 Jun 2008 22:14:09 +0100 1489618 http://www.medworm.com/index.php?rid=1489617&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F473603 In the dermis, fibroblasts play an important role in the turnover of the dermal extracellular matrix. Collagen I and III, the most important dermal proteins of the extracellular matrix, are progressively altered during ageing and diabetes. For mimicking diabetic conditions, the cultured human dermal fibroblasts were incubated with increasing amounts of AGE-modified BSA and D-glucose for 24 hours. The expression of procollagen α2(I) and procollagen α1(III) mRNA was analyzed by quantitative real-time PCR. Our data revealed that the treatment of fibroblasts with AGE-modified BSA upregulated the expression of procollagen α2(I) and procollagen α1(III) mRNA in a dose-dependent manner. High glucose levels mildly induced a profibrogenic pattern, increasing the procollag... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489617 Tue, 03 Jun 2008 22:14:09 +0100 1489617 http://www.medworm.com/index.php?rid=1489616&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F819123 Patients with fulminant type 1 diabetes almost completely lack C-peptide even soon after the onset of the disease, and the deficiency continues for the rest of their life. Thus, fulminant type 1 diabetes could serve as a good model of nature to explore the physiological role of C-peptide. For example, patients with fulminant type 1 diabetes have diabetic chronic complications more frequently than those with classical autoimmune type 1 diabetes 5 years after the onset of diabetes, and the higher prevalence could be partly attributable to the complete lack of C-peptide in fulminant type 1 diabetes. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489616 Tue, 03 Jun 2008 22:14:09 +0100 1489616 http://www.medworm.com/index.php?rid=1489615&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F230458 Diabetic polyneuropathy (DPN) occurs more frequently in type 1 diabetes resulting in a more severe DPN. The differences in DPN between the two types of diabetes are due to differences in the availability of insulin and C-peptide. Insulin and C-peptide provide gene regulatory effects on neurotrophic factors with effects on axonal cytoskeletal proteins and nerve fiber integrity. A significant abnormality in type 1 DPN is nodal degeneration. In the type 1 BB/Wor-rat, C-peptide replacement corrects metabolic abnormalities ameliorating the acute nerve conduction defect. It corrects abnormalities of neurotrophic factors and the expression of neuroskeletal proteins with improvements of axonal size and function. C-peptide corrects the expression of nodal adhesive molecules with prevention and repa... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489615 Tue, 03 Jun 2008 22:14:09 +0100 1489615 http://www.medworm.com/index.php?rid=1489614&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F371716 An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies sh... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489614 Tue, 03 Jun 2008 22:14:09 +0100 1489614 http://www.medworm.com/index.php?rid=1489613&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F730594 Conclusion/interpretation. C-peptide and its C-terminal fragments are equally effective in improving erythrocyte deformability in type 1 diabetes. The C-terminal residues of C-peptide are causally involved in this effect. The signal transduction pathway is Ca2+-dependent and involves activation of red blood cell Na+,K+-ATPase. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489613 Tue, 03 Jun 2008 22:14:09 +0100 1489613 http://www.medworm.com/index.php?rid=1489612&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F421287 The presence of fibrillar protein deposits (amyloid) of human islet amyloid polypeptide (hIAPP) in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet β-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-induced β-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of β-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer_s disease, Parkinson's disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489612 Tue, 03 Jun 2008 22:14:09 +0100 1489612 http://www.medworm.com/index.php?rid=1489611&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F697035 In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process. (Source: Experimental Diabetes Research) Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489611 Tue, 03 Jun 2008 22:14:09 +0100 1489611 http://www.medworm.com/index.php?rid=1489610&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F576862 Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its b... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489610 Tue, 03 Jun 2008 22:14:09 +0100 1489610 http://www.medworm.com/index.php?rid=1489609&cid=s_37026_15_f&fid=37026&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F281536 The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studi... Experimental Diabetes Research journals http://www.medworm.com/rss/comments.php?id=1489609 Tue, 03 Jun 2008 22:14:09 +0100 1489609