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CorrigendumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Tags: CORRIGENDA Source Type: journals

Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but th...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Jiao, Q., Pruznak, A. M., Huber, D., Vary, T. C., Lang, C. H. Tags: Articles Source Type: journals

Sex differences in the regulation of Kiss1/NKB neurons in juvenile mice: implications for the timing of pubertyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mammals, puberty onset typically occurs earlier in females than in males, but the explanation for sexual differentiation in the tempo of pubertal development is unknown. Puberty in both sexes is a brain-dependent phenomenon and involves alterations in the sensitivity of neuronal circuits to gonadal steroid feedback as well as gonadal hormone-independent changes in neuronal circuitry. Kisspeptin, encoded by the Kiss1 gene, plays an essential but ill-defined role in pubertal maturation. Neurokinin B (NKB) is coexpressed with Kiss1 in the arcuate nucleus (ARC) and is also important for puberty. We tested whether sex differ...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Kauffman, A. S., Navarro, V. M., Kim, J., Clifton, D. K., Steiner, R. A. Tags: Articles Source Type: journals

The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and {beta}-cell dysfunction in overweight and obese nondiabetic menEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prolonged elevation of plasma nonesterified fatty acids (NEFA) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. Studies in rodents suggest that inflammation may play a role in this "lipotoxicity." We studied the effects of sodium salicylate, an anti-inflammatory agent, on lipid-induced alterations in β-cell function and insulin sensitivity in six overweight and obese nondiabetic men. Each subject underwent four separate studies, 4–6 wk apart, in random order: 1) SAL, 1-wk placebo followed by intravenous (iv) infusion of saline for 48 h; 2) IH, 1-wk placebo followed ...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Xiao, C., Giacca, A., Lewis, G. F. Tags: Articles Source Type: journals

A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight lossEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin a...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Badman, M. K., Kennedy, A. R., Adams, A. C., Pissios, P., Maratos-Flier, E. Tags: Articles Source Type: journals

Nitric oxides mediates a shift from early necrosis to late apoptosis in cytokine-treated {beta}-cells that is associated with irreversible DNA damageEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This report tests the hypothesis that cell death mediated by nitric oxide shifts from an early necrotic to a late apoptotic event. Central to this transition is the ability of β-cells to respond and repair nitric oxide-mediated damage. β-Cells have the ability to repair DNA that is damaged following 24-h incubation with IL-1; however, cytokine-induced DNA damage becomes irreversible following 36-h incubation. This irreversible DNA damage following 36-h incubation with IL-1 correlates with the activation of caspase-3 (cleavage and activity). The increase in caspase activity correlates with reductions in endogenous...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Hughes, K. J., Chambers, K. T., Meares, G. P., Corbett, J. A. Tags: Articles Source Type: journals

Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we examined whether the activation of SIRT1, a mammalian ortholog of sirtuin, may ameliorate the development of NAFLD. Monosodium glutamate (MSG) mice, which exhibited obesity and insulin resistance, were treated with SRT1720, a specific SIRT1 activator from the age of 6–16 wk. Sixteen-week-old MSG mice exhibited increased liver triglyceride content and elevated levels of aminotransferase. SRT1720 treatment significantly reduced these levels without affecting body weight or food intake. These results suggested that the administration of SRT1720 ameliorated the development of NAFLD in MSG mice. The expr...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Yamazaki, Y., Usui, I., Kanatani, Y., Matsuya, Y., Tsuneyama, K., Fujisaka, S., Bukhari, A., Suzuki, H., Senda, S., Imanishi, S., Hirata, K., Ishiki, M., Hayashi, R., Urakaze, M., Nemoto, H., Kobayashi, M., Tobe, K. Tags: Articles Source Type: journals

Fetal liver X receptor activation acutely induces lipogenesis but does not affect plasma lipid response to a high-fat diet in adult miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There is increasing evidence that the metabolic state of the mother during pregnancy affects long-term glucose and lipid metabolism of the offspring. The liver X receptors (LXR) and -β are key regulators of cholesterol, fatty acid, and glucose metabolism. LXRs are activated by oxysterols and expressed in fetal mouse liver from day 10 of gestation onward. In the present study, we aimed to elucidate whether in utero pharmacological activation of LXR would influence fetal fatty acid and glucose metabolism and whether this would affect lipid homeostasis at adult age. Exposure of pregnant mice to the synthetic LXR agonist ...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: van Straten, E. M. E., van Meer, H., Huijkman, N. C. A., van Dijk, T. H., Baller, J. F. W., Verkade, H. J., Kuipers, F., Plosch, T. Tags: Articles Source Type: journals

Effects of the cannabinoid CB1 antagonist rimonabant on hepatic mitochondrial function in rats fed a high-fat dietEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim of this study was to investigate the effect of rimonabant treatment on hepatic mitochondrial function in rats fed a high-fat diet. Sprague-Dawley rats fed a high-fat diet (35% lard) for 13 wk were treated with rimonabant (10 mg·kg–1·day–1) during the last 3 wk and matched with pair-fed controls. Oxygen consumption with various substrates, mitochondrial enzyme activities on isolated liver mitochondria, and mitochondrial DNA quantity were determined. Body weight and fat mass were decreased in rats treated with rimonabant compared with pair-fed controls. Moreover, the serum adiponectin level ...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Flamment, M., Gueguen, N., Wetterwald, C., Simard, G., Malthiery, Y., Ducluzeau, P.-H. Tags: Articles Source Type: journals

Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese womenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1β, IL-10, TNF, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Siklova-Vitkova, M., Polak, J., Klimcakova, E., Vrzalova, J., Hejnova, J., Kovacikova, M., Kovacova, Z., Bajzova, M., Rossmeislova, L., Hnevkovska, Z., Langin, D., Stich, V. Tags: Articles Source Type: journals

Impact of type 1 diabetes on cardiac fibroblast activation: enhanced cell cycle progression and reduced myofibroblast content in diabetic myocardiumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Diabetic patients are prone to developing myocardial fibrosis and suffer from decreased wound healing capabilities. The purpose of this study was to determine whether diabetes alters cardiac fibroblast activity in the myocardium in a 6-wk streptozotocin-induced type 1 diabetic model. In vivo echocardiography indicated significant dilation of the left ventricle (LV) in the diabetic animals, while cardiac function was comparable to that in the normal group. We isolated cardiac fibroblasts from diabetic and control hearts and observed increased proliferation of the diabetic fibroblasts. Microarray analysis using mRNA collecte...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Shamhart, P. E., Luther, D. J., Hodson, B. R., Koshy, J. C., Ohanyan, V., Meszaros, J. G. Tags: Articles Source Type: journals

Novel liver-specific TORC2 siRNA corrects hyperglycemia in rodent models of type 2 diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, these results demonstrate the importance of TORC2 in modulating HGP in vivo and highlight a novel, liver-specific siRNA approach for the potential treatment of hyperglycemia and type 2 diabetes. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Saberi, M., Bjelica, D., Schenk, S., Imamura, T., Bandyopadhyay, G., Li, P., Jadhar, V., Vargeese, C., Wang, W., Bowman, K., Zhang, Y., Polisky, B., Olefsky, J. M. Tags: Articles Source Type: journals

TIP39/parathyroid hormone type 2 receptor signaling is a potent inhibitor of chondrocyte proliferation and differentiationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tuberoinfundibular peptide of 39 residues (TIP39) is a member of the parathyroid hormone (PTH) family of peptide hormones that exerts its function by interacting with the PTH type 2 receptor (PTH2R). Presently, no known function has been attributed to this signaling pathway in the developing skeleton. We observed that TIP39 and PTH2R were present in the newborn mouse growth plate, with the receptor localizing in the resting zone whereas ligand expression was restricted exclusively in prehypertrophic and hypertrophic chondrocytes. By 8 wk of life, PTH2R, and to a lesser degree TIP39, immunoreactivity was present in articula...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Panda, D., Goltzman, D., Juppner, H., Karaplis, A. C. Tags: Articles Source Type: journals

Effects of hormone-sensitive lipase disruption on cardiac energy metabolism in response to fasting and refeedingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Increased fatty acid (FA) flux and intracellular lipid accumulation (steatosis) give rise to cardiac lipotoxicity in both pathological and physiological conditions. Since hormone-sensitive lipase (HSL) contributes to intracellular lipolysis in adipose tissue and heart, we investigated the impact of HSL disruption on cardiac energy metabolism in response to fasting and refeeding. HSL-knockout (KO) mice and wild-type (WT) littermates were fasted for 24 h, followed by ~6 h of refeeding. Plasma FA concentration in WT mice was elevated twofold with fasting, whereas KO mice lacked this elevation, resulting in twofold lower cardi...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Suzuki, J., Ueno, M., Uno, M., Hirose, Y., Zenimaru, Y., Takahashi, S., Osuga, J.-i., Ishibashi, S., Takahashi, M., Hirose, M., Yamada, M., Kraemer, F. B., Miyamori, I. Tags: Articles Source Type: journals

Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models--association with liver and adipose tissue effectsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recombinant fibroblast growth factor (FGF)21 has antihyperglycemic, antihyperlipidemic, and antiobesity effects in diabetic rodent and monkey models. Previous studies were confined to measuring steady-state effects of FGF21 following subchronic or chronic administration. The present study focuses on the kinetics of biological actions of FGF21 following a single injection and on the associated physiological and cellular mechanisms underlying FGF21 actions. We show that FGF21 resulted in rapid decline of blood glucose levels and immediate improvement of glucose tolerance and insulin sensitivity in two animal models of insuli...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Xu, J., Stanislaus, S., Chinookoswong, N., Lau, Y. Y., Hager, T., Patel, J., Ge, H., Weiszmann, J., Lu, S.-C., Graham, M., Busby, J., Hecht, R., Li, Y.-S., Li, Y., Lindberg, R., Veniant, M. M. Tags: Articles Source Type: journals

A rosiglitazone-induced increase in adiponectin does not improve glucose metabolism in HIV-infected patients with overt lipoatrophyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HIV-infected patients on antiretroviral therapy frequently develop changes in body fat distribution and disturbances in glucose metabolism, associated with reduced adiponectin levels. Because adiponectin, principally the high-molecular-weight (HMW) form, has insulin-sensitizing properties, we investigated the effects of an increase in adiponectin on glucose metabolism in HIV-lipodystrophy. In this randomized, double-blind, placebo-controlled trial, we included HIV-1-infected patients with severe lipoatrophy, with an undetectable viral load and who had received neither protease inhibitors nor stavudine for ≥6 mo. Patient...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Blumer, R. M. E., van der Valk, M., Ackermans, M., Endert, E., Serlie, M. J., Reiss, P., Sauerwein, H. P. Tags: Articles Source Type: journals

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined possible nongenomic effects of progesterone in breast epithelia by using MCF-10A cells known to lack nuclear progesterone receptor expression. Treatment for 30–60 min with progesterone or the progestin, R5020, increased mitochondrial activity as shown by an increase in mitochondrial membrane potential (hyperpolarization) with a concordant increase in total cellular ATP. The reaction was inhibited by a specific progesterone receptor antagonist and not affected by the translation inhibitor cycloheximide. Progestin treatment inhibited apoptosis induced by activation of the FasL pathway, as shown by a...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Behera, M. A., Dai, Q., Garde, R., Saner, C., Jungheim, E., Price, T. M. Tags: Articles Source Type: journals

Differential efficacy of SSTR1, -2, and -5 agonists in the inhibition of C6 glioma growth in nude miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Somatostatin receptors (SSTR1–5) mediate antiproliferative effects. In C6 rat glioma cells, somatostatin is cytostatic in vitro via phosphotyrosine phosphatase-dependent inhibition of ERK1/2 activity mediated by SSTR1, -2, and -5. Here we analyzed the effects of SSTR activation on C6 glioma growth in vivo and the intracellular mechanisms involved, comparing somatostatin effects with selective agonists for SSTR1, -2, and -5 (BIM-23745, BIM-23120, BIM-23206) or receptor biselective compounds (SSTR1 and -2, BIM-23704; and SSTR2 and -5, BIM-23190). Nude mice subcutaneously xenografted with C6 cells were treated with soma...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Barbieri, F., Pattarozzi, A., Gatti, M., Aiello, C., Quintero, A., Lunardi, G., Bajetto, A., Ferrari, A., Culler, M. D., Florio, T. Tags: Articles Source Type: journals

Overexpression of the nuclear factor-{kappa}B subunit c-Rel protects against human islet cell death in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transcription factor nuclear factor (NF)-B is known to modulate rates of apoptosis and may therefore play a role in the increased β-cell death that occurs in type 1 and type 2 diabetes. The aim of the present investigation was to study the expression of NF-B subunits in human islet cells and whether overexpression of the NF-B subunit c-Rel affects islet cell survival. We detected expression of p65, Rel-B, p50, p105, p52, and the ribosomal protein S3 (rpS3) in human islet cells. Among these, only p65 and rpS3 were translocated from the cytosolic to the nuclear fraction in response to cytokines. Interestingly, rpS3 ...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Mokhtari, D., Barbu, A., Mehmeti, I., Vercamer, C., Welsh, N. Tags: Articles Source Type: journals

Restoring AS160 phosphorylation rescues skeletal muscle insulin resistance and fatty acid oxidation while not reducing intramuscular lipidsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, despite the maintenance of high concentrations of palmitate (2 mM), as well as increased concentrations of intramuscular lipids (triacylglycerol, diacylglycerol, and ceramide), the rapid AICAR- and leptin-mediated rescue of palmitate-induced insulin resistance is attributable to the restoration of insulin-stimulated AS160 phosphorylation and GLUT4 translocation. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Alkhateeb, H., Chabowski, A., Glatz, J. F. C., Gurd, B., Luiken, J. J. F. P., Bonen, A. Tags: Articles Source Type: journals

Ontogeny of methionine utilization and splanchnic uptake in critically ill childrenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
To determine the rates of methionine splanchnic uptake and utilization in critically ill pediatric patients we used two kinetic models: the plasma methionine enrichment and the "intracellular" homocysteine enrichment. Twenty four patients, eight infants, eight children, and eight adolescents, were studied. They received simultaneous, primed, constant, intravenous infusions of l-[2H3]methylmethionine and enteral l-[1-13C]methionine. The ratio of [13C]homocysteine to [13C]methionine enrichment was 1.0 ± 0.15, 0.80 ± 0.20, and 0.66 ± 0.10, respectively, for the infants, children, and adolescents, and it w...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Verbruggen, S., Sy, J., Gordon, W. E., Hsu, J., Wu, M., Chacko, S., Zurakowski, D., Burrin, D., Castillo, L. Tags: Articles Source Type: journals

Effects of hypoxia on testosterone release in rat Leydig cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim of this study was to explore the effect and action mechanisms of intermittent hypoxia on the production of testosterone both in vivo and in vitro. Male rats were housed in a hypoxic chamber (12% O2 + 88% N2, 1.5 l/ml) 8 h/day for 4 days. Normoxic rats were used as control. In an in vivo experiment, hypoxic and normoxic rats were euthanized and the blood samples collected. In the in vitro experiment, the enzymatically dispersed rat Leydig cells were prepared and challenged with forskolin (an adenylyl cyclase activator, 10–4 M), 8-Br-cAMP (a membrane-permeable analog of cAMP, 10–4 M), hCG (0.05 IU), the p...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Hwang, G.-S., Chen, S.-T., Chen, T.-J., Wang, S.-W. Tags: Articles Source Type: journals

Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study attempted to define the role of hepatic Niemann-Pick C1-like 1 (NPC1L1), a cholesterol transporter, in hepatic insulin resistance as well as hepatic steatosis. The inhibition of NPC1L1 and its molecular consequences were examined in Zucker obese fatty (ZOF) rats and cultured steatotic hepatocytes using ezetimibe, a pharmacoloigcal inhibitor of NPC1L1, and short hairpin RNA (shRNA) of NPC1L1. Ezetimibe improved hepatic insulin signaling as well as hepatic steatosis in ZOF rats. It also restored insulin sensitivity in steatotic hepatocytes in vitro through a reduction in hepatic reactive oxygen species (ROS...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Nomura, M., Ishii, H., Kawakami, A., Yoshida, M. Tags: Articles Source Type: journals

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Muniyappa, R., Chen, H., Muzumdar, R. H., Einstein, F. H., Yan, X., Yue, L. Q., Barzilai, N., Quon, M. J. Tags: Articles Source Type: journals

Critical roles for the TSC-mTOR pathway in {beta}-cell functionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TSC1 is a tumor suppressor that associates with TSC2 to inactivate Rheb, thereby inhibiting signaling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as translation, in response to growth factors and nutrient signals. To test roles for TSC1 and mTORC1 in β-cell function, we utilized Rip2/Cre to generate mice lacking Tsc1 in pancreatic β-cells (Rip-Tsc1cKO mice). Although obesity developed due to hypothalamic Tsc1 excision in older Rip-Tsc1cKO animals, young animals displayed a prominent gain-of-function β-cell phenot...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Mori, H., Inoki, K., Opland, D., Munzberg, H., Villanueva, E. C., Faouzi, M., Ikenoue, T., Kwiatkowski, D. J., MacDougald, O. A., Myers, M. G., Guan, K.-L. Tags: Articles Source Type: journals

Role of lipid-derived mediators in skeletal muscle insulin resistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Imbalance between nutritional intake and energy expenditure has been described to culminate in obesity, which predisposes to insulin resistance and type 2 diabetes mellitus. In such states of energy oversupply, excess amounts of lipids are available in tissues and circulation. Over the past years, an increasingly important role in development of skeletal muscle (SkM) insulin resistance has been attributed to lipids and impaired fatty acid metabolism. In this review, we reflect the current state of knowledge about the effects of various lipid-derived mediators on SkM insulin sensitivity. Furthermore, potential mechanisms un...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Taube, A., Eckardt, K., Eckel, J. Tags: Reviews Source Type: journals

Inflammation and impaired adipogenesis in hypertrophic obesity in manEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differenti...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Gustafson, B., Gogg, S., Hedjazifar, S., Jenndahl, L., Hammarstedt, A., Smith, U. Tags: Reviews Source Type: journals

The origin of intermuscular adipose tissue and its pathophysiological implicationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The intermuscular adipose tissue (IMAT) is a depot of adipocytes located between muscle bundles. Several investigations have recently been carried out to define the phenotype, the functional characteristics, and the origin of the adipocytes present in this depot. Among the different mechanisms that could be responsible for the accumulation of fat in this site, the dysdifferentiation of muscle-derived stem cells or other mesenchymal progenitors has been postulated, turning them into cells with an adipocyte phenotype. In particular, muscle satellite cells (SCs), a heterogeneous stem cell population characterized by plasticit...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Vettor, R., Milan, G., Franzin, C., Sanna, M., De Coppi, P., Rizzuto, R., Federspil, G. Tags: Reviews Source Type: journals

Transdifferentiation properties of adipocytes in the adipose organEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plastici...
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Cinti, S. Tags: Reviews Source Type: journals

Adipose tissue function and dysfunction: organ cross talk and metabolic riskEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 21, 2009 Category: Endocrinology Authors: Giorgino, F. Tags: Editorial Focus Source Type: journals

UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPKEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined the role of UCF-101 on streptozotocin (STZ)-induced diabetic heart defect. Vehicle or UCF-101 was administrated to STZ diabetic mice, and cardiomyocyte mechanical properties were analyzed. UCF-101 reduced STZ-induced hyperglycemia and alleviated STZ-induced aberration in cardiomyocyte contractile mechanics. Diabetes dramatically decreased AMPK phosphorylation at Thr172 of catalytic -subunit, which was restored by UCF-101. Neither diabetes nor UCF-101 affected the expression of HtrA2/Omi and XIAP or caspase-3 activity. The AMPK activator resveratrol mimicked the UCF-101-induced beneficial effect against ...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Li, Q., Li, J., Ren, J. Tags: Articles Source Type: journals

Genetic and metabolic effects on skeletal muscle AMPK in young and older twinsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The protein complex AMP-activated protein kinase (AMPK) is believed to play an important role in the regulation of skeletal muscle glucose and lipid metabolism. Defects in the AMPK system might therefore be an important factor in the pathogenesis of type 2 diabetes. We aimed to identify genetic and environmental mechanisms involved in the regulation of AMPK expression and activity and to examine the association between AMPK protein levels and activity on the one hand, and glucose and fat metabolism on the other. We investigated skeletal muscle biopsies from 100 young and 82 older mono- and dizygotic nondiabetic twins excis...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Mortensen, B., Poulsen, P., Wegner, L., Stender-Petersen, K. L., Ribel-Madsen, R., Friedrichsen, M., Birk, J. B., Vaag, A., Wojtaszewski, J. F. P. Tags: Articles Source Type: journals

Role of CYP27A1 in progesterone metabolism in vitro and in vivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the kidney, progesterone is inactivated to 20-dihydro-progesterone (20-DH-progesterone) to protect the mineralocorticoid receptor from progesterone excess. In an attempt to clone the enzyme with 20-hydroxysteroid activity using expression cloning in CHOP cells and a human kidney expression library, serendipitously cDNA encoding CYP27A1 was isolated. Overexpression of CYP27A1 in CHOP cells decreased progesterone conversion to 20-DH-progesterone in a dose-dependent manner, an effect enhanced by cotransfection with adrenodoxin and adrenodoxin reductase. Incubation of CHOP cells with 27-hydroxycholesterol, a product of CYP2...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Escher, G., Vogeli, I., Escher, R., Tuckey, R. C., Erickson, S., Krozowski, Z., Frey, F. J. Tags: Articles Source Type: journals

Minimal model assessment of hepatic insulin extraction during an oral test from standard insulin kinetic parametersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this article, a first aim was to develop a minimal modeling approach to noninvasively assess hepatic insulin extraction in 204 healthy subjects studied with a standard meal by coupling the already available meal C-peptide minimal model with a new insulin model. The ingredients of this model are posthepatic IDR, which in turn is described in terms of pancreatic ISR and hepatic insulin extraction HE, and a linear monocompartmental model of insulin kinetics. Even if ISR is provided by the C-peptide minimal model, the simultaneous assessment of HE and insulin kinetics is critical, since compensations may arise between param...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Campioni, M., Toffolo, G., Basu, R., Rizza, R. A., Cobelli, C. Tags: Articles Source Type: journals

Relation between extent of myostatin depletion and muscle growth in mature miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myostatin is a negative regulator of muscle growth and fiber size. Changes in myostatin expression might contribute to changes in muscle mass associated with various conditions, and reducing the amount of active myostatin is a potential strategy for preventing or reversing muscle atrophy. The present study was done to determine the extent to which myostatin levels must decline to induce growth of mature muscles. Myostatin expression was reduced by activating Cre recombinase in adult mice with floxed myostatin genes. The duration of Cre activation varied from 1 to 6 wk, and the residual myostatin mRNA expression after Cre a...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Welle, S., Burgess, K., Thornton, C. A., Tawil, R. Tags: Articles Source Type: journals

Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Some studies suggest that the 5'-AMP-activated protein kinase (AMPK) is important in regulating muscle glucose uptake in response to intense electrically stimulated contractions. However, it is unknown whether AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male and female mice overexpressing kinase-dead AMPK2 (AMPK-KD) in skeletal and heart muscles. Wild-type and AMPK-KD mice were exercised at the same absolute intensity and the same relative intensity (30 and 70% of individual maximal running speed) to correct for reduced exercise capacity of the AMPK-KD mouse. Muscle glucose clearance wa...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Maarbjerg, S. J., Jorgensen, S. B., Rose, A. J., Jeppesen, J., Jensen, T. E., Treebak, J. T., Birk, J. B., Schjerling, P., Wojtaszewski, J. F. P., Richter, E. A. Tags: Articles Source Type: journals

The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The calcium-sensing receptor (CaSR) controls parathyroid hormone (PTH) secretion, which, in turn, via direct and indirect actions on kidney, bone, and intestine, maintains a normal extracellular ionized calcium concentration (Ca2+o). There is less understanding of the CaSR's homeostatic importance outside of the parathyroid gland. We have employed single and double knockout mouse models, namely mice lacking PTH alone (CaSR+/+ PTH–/–, referred to as C+P–), lacking both CaSR and PTH (CaSR–/– PTH–/–, C–P–) or wild-type (CaSR+/+ PTH+/+, C+P+) mice to study CaSR-specific fun...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Kantham, L., Quinn, S. J., Egbuna, O. I., Baxi, K., Butters, R., Pang, J. L., Pollak, M. R., Goltzman, D., Brown, E. M. Tags: Articles Source Type: journals

Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sertoli cells provide the physical support and the necessary environment for germ cell development. Among the products secreted by Sertoli cells, lactate, the preferred energy substrate for spermatocytes and spermatids, is present. Considering the essential role of lactate on germ cell metabolism, it is supposed that Sertoli cells must ensure its production even in adverse conditions, such as those that would result from a decrease in glucose levels in the extracellular milieu. The aim of the present study was to investigate 1) a possible effect of glucose deprivation on glucose uptake and on the expression of glucose tran...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Riera, M. F., Galardo, M. N., Pellizzari, E. H., Meroni, S. B., Cigorraga, S. B. Tags: Articles Source Type: journals

Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we found that the basal Akt phosphorylation level was increased in liver and gastrocnemius of mice under the high-fat diet (HFD). Levels of mitochondrial DNA and expression of some mitochondrion-associated genes were decreased by the HFD primarily in liver. Triglyceride content was increased in both liver and gastrocnemius by the HFD. Oxidative stress was induced by the HFD in both liver and gastrocnemius. Insulin sensitivity was decreased by the HFD. All of these changes were largely or completely reversed by treatment of animals with the phosphatidylinositol 3-kinase inhibitor LY-294002 during the time whe...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Liu, H.-Y., Hong, T., Wen, G.-B., Han, J., Zuo, D., Liu, Z., Cao, W. Tags: Articles Source Type: journals

Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic peopleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, acute insulin deprivation caused both a decrease and increase in synthesis rates of many plasma proteins with various functions. Moreover, chronic systemic insulin treatment not only did not normalize synthesis of all plasma proteins but also altered synthesis of several additional proteins that were unaltered during insulin deprivation. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Jaleel, A., Klaus, K. A., Morse, D. M., Karakelides, H., Ward, L. E., Irving, B. A., Nair, K. S. Tags: Articles Source Type: journals

Mechanisms to conserve glucose in lactating women during a 42-h fastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to determine whether lactating women conserve plasma glucose by reducing maternal glucose utilization by increasing utilization of FFA and ketone bodies and/or increasing gluconeogenesis and mammary gland hexoneogenesis. Six healthy exclusively breastfeeding women and six nonlactating controls were studied during 42 h of fasting and 6 h of refeeding. Glucose and protein kinetic parameters were measured using stable isotopes and GCMS and energy expenditure and substrate oxidation using indirect calorimetry. After 42 h of fasting, milk production decreased by 16% but remained within normal ran...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Mohammad, M. A., Sunehag, A. L., Chacko, S. K., Pontius, A. S., Maningat, P. D., Haymond, M. W. Tags: Articles Source Type: journals

Characterization of contraction-inducible CXC chemokines and their roles in C2C12 myocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Physical exercise triggers the release of several cytokines/chemokines from working skeletal muscles, but the underlying mechanism(s) by which skeletal muscles decipher and respond to highly complex contractile stimuli remains largely unknown. In an effort to investigate the regulatory mechanisms of the expressions of two contraction-inducible CXC chemokines, CXCL1/KC and CXCL5/LIX, in contracting skeletal muscle cells, we took advantage of our in vitro exercise model using highly developed contractile C2C12 myotubes, which acquire properties similar to those of in vivo skeletal muscle via manipulation of Ca2+ transients w...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Nedachi, T., Hatakeyama, H., Kono, T., Sato, M., Kanzaki, M. Tags: Articles Source Type: journals

Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent–/–) mouse. Ent–/– mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent–/– mice develop diet-induced obesity, as...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Miller, R., D'Agostino, D., Erlanson-Albertsson, C., Lowe, M. E. Tags: Articles Source Type: journals

NIH experiment in centralized mouse phenotyping: the Vanderbilt experience and recommendations for evaluating glucose homeostasis in the mouseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article addresses two topics. We provide an overview of the National Institutes of Health Mouse Metabolic Phenotyping Center (MMPC) Program. We then discuss some observations we have made during the first eight years of the Vanderbilt MMPC regarding common phenotyping practices. We include specific recommendations to improve phenotyping practices for tests of glucose tolerance and insulin action. We recommend that methods for experiments in vivo be described in manuscripts. We make specific recommendations for data presentation, interpretation, and experimental design for each test. To facilitate and maximize the exch...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: McGuinness, O. P., Ayala, J. E., Laughlin, M. R., Wasserman, D. H. Tags: Review Source Type: journals

Will the original glucose transporter isoform please stand up!Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monosaccharides enter cells by slow translipid bilayer diffusion by rapid, protein-mediated, cation-dependent cotransport and by rapid, protein-mediated equilibrative transport. This review addresses protein-mediated, equilibrative glucose transport catalyzed by GLUT1, the first equilibrative glucose transporter to be identified, purified, and cloned. GLUT1 is a polytopic, membrane-spanning protein that is one of 13 members of the human equilibrative glucose transport protein family. We review GLUT1 catalytic and ligand-binding properties and interpret these behaviors in the context of several putative mechanisms for prote...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Carruthers, A., DeZutter, J., Ganguly, A., Devaskar, S. U. Tags: Review Source Type: journals

Facilitative glucose transporter 9, a unique hexose and urate transporterEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GLUT9 is a novel, facilitative glucose transporter isoform that exists as two alternative splice variants encoding two proteins that differ in their NH2-terminal sequence (GLUT9a and GLUT9b). Both forms of GLUT9 protein and mRNA are expressed in the epithelia of various tissues; however, the two splice variants are expressed differentially within polarized cells, with GLUT9a localized predominantly on the basolateral surfaces and GLUT9b expressed on apical surfaces. Protein expression of GLUT9 drops under conditions of starvation but increases with addition of glucose and under hyperglycemic conditions. The substrate speci...
Source: AJP: Endocrinology and Metabolism - September 23, 2009 Category: Endocrinology Authors: Doblado, M., Moley, K. H. Tags: Review Source Type: journals

Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in Xenopus oocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The System L transporter facilitates cellular import of large neutral amino acids (AAs) such as Leu, a potent activator of the intracellular target of rapamycin (TOR) pathway, which signals for cell growth. System L is an AA exchanger, proposed to accumulate certain AAs by coupling to dissipation of concentration gradient(s) of exchange substrates generated by secondary active AA transporters such as System A (SNAT2). We addressed the hypothesis that this type of coupling (termed tertiary active transport) acts as an indirect mechanism to extend the range of AA stimulating TOR to those transported by both Systems A and L (...
Source: AJP: Endocrinology and Metabolism - August 17, 2009 Category: Endocrinology Authors: Baird, F. E., Bett, K. J., MacLean, C., Tee, A. R., Hundal, H. S., Taylor, P. M. Tags: ARTICLES Source Type: journals

ERp46 is reduced by high glucose and regulates insulin content in pancreatic {beta}-cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Our studies focus on ERp46, an endoplasmic reticulum (ER) component, and analyze its involvement in glucose toxicity and in insulin production. Differences in pancreatic β-TC-6 cell proteome under conditions of low vs. high glucose were examined by proteomic approaches, including two-dimensional gel electrophoresis, image analysis, and mass spectrometry. Among differentially expressed proteins, ERp46, a novel endoplasmic reticulum component, was examined further. The expression of ERp46 in pancreatic sections was analyzed by immunocytochemistry, and high glucose-induced alterations of expression were evaluated in cult...
Source: AJP: Endocrinology and Metabolism - August 17, 2009 Category: Endocrinology Authors: Alberti, A., Karamessinis, P., Peroulis, M., Kypreou, K., Kavvadas, P., Pagakis, S., Politis, P. K., Charonis, A. Tags: ARTICLES Source Type: journals

A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intoleranceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ghrelin is a stomach-derived peptide that has growth hormone-stimulating and orexigenic activities. Although there have been several reports of ghrelinoma cases, only a few cases have elevated circulating ghrelin levels, hampering the investigation of pathophysiological features of ghrelinoma and chronic effects of ghrelin excess. Furthermore, standard transgenic technique has resulted in desacyl ghrelin production only because of the limited tissue expression of ghrelin O-acyltransferase, which mediates acylation of ghrelin. Accordingly, we attempted to create ghrelin promoter SV40 T-antigen transgenic (GP-Tag Tg) mice, i...
Source: AJP: Endocrinology and Metabolism - August 17, 2009 Category: Endocrinology Authors: Iwakura, H., Ariyasu, H., Li, Y., Kanamoto, N., Bando, M., Yamada, G., Hosoda, H., Hosoda, K., Shimatsu, A., Nakao, K., Kangawa, K., Akamizu, T. Tags: ARTICLES Source Type: journals

Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets responsible for the degradation of proteoglycans such as perlecan and dermatan sulfate. Previous findings of our group demonstrated the involvement of IDS in the normal pathway of lysosomal degradation of secretory peptides, suggesting a role of this enzyme in β-cell secretory functionality. The present study was undertaken to characterize the effect of IDS overexpression on insulin release. INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detec...
Source: AJP: Endocrinology and Metabolism - August 17, 2009 Category: Endocrinology Authors: Piquer, S., Casas, S., Quesada, I., Nadal, A., Julia, M., Novials, A., Gomis, R. Tags: ARTICLES Source Type: journals