Incretin TherapyThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

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Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Objective: To examine after gastric bypass the effect of peroral vs. gastroduodenal feeding on glucose metabolism. Research Design and Methods: A type 2 diabetic patient was examined on two consecutive days 5 weeks after gastric bypass. A standard liquid meal was given, on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C peptide, glucagon, incretin hormones, peptide YY and free fatty acids were measured. Results: Peroral feeding reduced 2-h-postprandial plasma glucose (7.8 vs. 11.1 mM) and incremental-area-under-the-glucose-curve (0.33 vs. 0.49 mMxmin) compared...
Source: Diabetes Care - November 16, 2009 Category: Endocrinology Authors: Dirksen C, Hansen DL, Madsbad S, Hvolris LE, Naver LS, Holst JJ, Worm D Tags: Diabetes Care Source Type: journals

Meal-Anticipatory Glucagon-Like Peptide-1 Secretion in Rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Animals anticipating a meal initiate a series of responses enabling them to better cope with the meal's metabolic impact. These responses, such as cephalic insulin, occur prior to the onset of ingestion and are especially evident in animals maintained on a meal-feeding schedule with limited but predictable access to food each day. We tested the hypothesis that meal-fed rats secrete the incretin hormone glucagon-like peptide-1 (GLP-1) cephalically when anticipating a large meal. Male Long-Evans rats were fed ad libitum (controls) or adapted to a schedule on which food was available for the same 4-h period each day (meal...
Source: Endocrinology - November 13, 2009 Category: Endocrinology Authors: Vahl TP, Drazen DL, Seeley RJ, D'Alessio DA, Woods SC Tags: Endocrinology Source Type: journals

Diabetes drug liraglutide 'better than orlistat and placebo for weight loss'Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A daily injection with liraglutide – the latest incretin drug for diabetes - is better at promoting weight loss than orlistat and placebo, alongside diet and exercise, a new study has found. (Source: Pulse)
Source: Pulse - October 26, 2009 Category: Primary Care Tags: News Source Type: news

A battle for controlEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Without a doubt, many patients require insulin. But some who have Type 2 disease resolve to change their lives instead. Simply put, diabetes is a contest between people and their blood. For people whose bodies don't produce enough insulin to manage their blood sugar, the goal is a normal blood score, achieved through a balancing act of lifestyle and medication. ¶ "Eventually most patients will follow a course of lifestyle, medications, then insulin," said Dr. Enrico Cagliero, referring to people diagnosed with the most common form of diabetes, known as Type 2. He's an endocr...
Source: L.A. Times - Health - October 24, 2009 Category: Consumer Health News Source Type: news

A BATTLE FOR CONTROL: Special issue on diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Without a doubt, many patients require insulin. But some who have Type 2 disease resolve to change their lives instead. Simply put, diabetes is a contest between people and their blood. For people whose bodies don't produce enough insulin to manage their blood sugar, the goal is a normal blood score, achieved through a balancing act of lifestyle and medication. ¶ "Eventually most patients will follow a course of lifestyle, medications, then insulin," said Dr. Enrico Cagliero, referring to people diagnosed with the most common form of diabetes, known as Type 2. He's an endocr...
Source: L.A. Times - Health - October 24, 2009 Category: Consumer Health News Source Type: news

Incretin therapy shows promiseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In experiments on rats, the gut hormones increased the number of insulin-producing cells in the pancreas. Physicians who treat diabetes consider incretin therapy one of the most exciting new tools that they've seen in a long time for combating the disease. (Source: L.A. Times - Health)
Source: L.A. Times - Health - October 24, 2009 Category: Consumer Health News Source Type: news

The Rho Guanosine 5'-Triphosphatase, Cell Division Cycle 42, Is Required for Insulin-Induced Actin Remodeling and Glucagon-Like Peptide-1 Secretion in the Intestinal Endocrine L Cell.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Rho GTPases, such as cell division cycle 42 (Cdc42) and ras-related C3 botulinum toxin substrate 1 (Rac1), have been identified as regulators of F-actin dynamics and hormone release from endocrine cells; however, their role in secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), from the enteroendocrine L cell is unknown. Insulin induced a 1.4-fold increase in L cell GLP-1 release; however, secretion was potentiated to 2.1-fold in the presence of the F-actin depolymerizing agent, latrunculin B, suggesting that F-actin functions as a permissive barrier. In murine GLUTag L cells, insulin stimulated F-actin...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Lim GE, Xu M, Sun J, Jin T, Brubaker PL Tags: Endocrinology Source Type: journals

Treating type 2 diabetes: incretin mimetics and enhancersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As a consequence of excess abdominal adiposity and genetic predisposition, type 2 diabetes is a progressive disease, often diagnosed after metabolic dysfunction has taken hold of multiple organ systems. Insulin deficiency, insulin resistance and impaired glucose homeostasis resulting from beta-cell dysfunction characterize the disease. Current treatment goals are often unmet due to insufficient treatment modalities. Even when combined, these treatment modalities are frequently limited by safety, tolerability, weight gain, edema and gastrointestinal intolerance. Recently, new therapeutic classes have become available for tr...
Source: Therapeutic Advances in Cardiovascular Disease - October 6, 2009 Category: Cardiology Authors: Nori Janosz, K. E., Zalesin, K. C., Miller, W. M., McCullough, P. A. Tags: Articles Source Type: journals

Sodium glucose co-transporter 1 (SGLT1) mediates glucose-induced incretin secretion in mice in vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glucose ingestion stimulates the secretion of the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Despite the critical role of incretins in glucose homeostasis, the mechanism of glucose induced incretin secretion has not been established. We investigated the underlying mechanism of glucose-induced incretin secretion in vivo in mice. Injection of glucose at 1 g/kg into the upper intestine significantly increased plasma GIP and GLP-1 levels, whereas injection of glucose into the colon did not increase GIP and GLP-1 levels. This finding indicates that the glucose sens...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 5, 2009 Category: Physiology Authors: Moriya R, Shirakura T, Ito J, Mashiko S, Seo T Tags: Am J Physiol Endocrinol Metab Source Type: journals

Effects of Exenatide Alone and in Combination with Daclizumab on Beta Cell Function in Long-Standing Type 1 Diabetes Mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions - In long-standing type 1 diabetes, which remains an active autoimmune disease even decades after its onset, surviving beta-cells secrete insulin in a physiologically regulated manner. However, the combination of intensified insulin therapy, exenatide, and daclizumab did not induce improved function of these remaining beta-cells. PMID: 19808924 [PubMed - as supplied by publisher] (Source: Diabetes Care)
Source: Diabetes Care - October 5, 2009 Category: Endocrinology Authors: Rother KI, Spain LM, Wesley RA, Digon BJ, Baron A, Chen K, Nelson P, Dosch HM, Palmer J, Brooks-Worrell B, Ring M, Harlan DM Tags: Diabetes Care Source Type: journals

EASD: Incretins Come of AgeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
VIENNA (MedPage Today) -- The latest information on incretin drugs for type 2 diabetes was the topic for this exclusive MedPage Today InFocus™ video discussion here at the European Association for the Study of Diabetes annual meeting. (Source: MedPage Today Cardiovascular)
Source: MedPage Today Cardiovascular - October 2, 2009 Category: Cardiology Source Type: news

[Occurrence of GRB10 (+11275G > A) polymorphism in Hungarian population and its relationship to glucose metabolism.]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
[Occurrence of GRB10 (+11275G > A) polymorphism in Hungarian population and its relationship to glucose metabolism.] Orv Hetil. 2009 Oct 1;150(40):1845-51 Authors: Vitai M, Buday B, Kulcsár E, Literáti-Nagy B, Vecsei I, Bezzegh K, Péterfai E, Kurucz I, Korányi L In our backstage experiment with differential display method among the differentially expressed genes we found the gene of GRB10 (Growth factor Receptor-Bound protein 10). The GRB10 protein binds to insulin and insulin-like growth factor receptors and acts as a negative regulatory protein. Besides, GRB10 gene polymorphisms are con...
Source: Orvosi Hetilap - September 30, 2009 Category: Journals (General) Authors: Vitai M, Buday B, Kulcsár E, Literáti-Nagy B, Vecsei I, Bezzegh K, Péterfai E, Kurucz I, Korányi L Tags: Orv Hetil Source Type: journals

Expression of glucose-dependent-insulinotropic polypeptide (gip) in the zebrafish.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, the results of these studies suggest that although the zebrafish appears to be a model of an early stage of evolutionary development of GIP expression, the peptide may not possess incretin properties in this species. Key words: incretin hormones, enteroinsular axis, endocrine pancreas. PMID: 19793957 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology)
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - September 29, 2009 Category: Physiology Authors: Musson MC, Jepeal LI, Mabray PD, Zhdanova IV, Cardoso WV, Wolfe MM Tags: Am J Physiol Regul Integr Comp Physiol Source Type: journals

New Therapeutic Horizons: Mapping the Future of Glycemic Control With Incretin-based TherapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion Currently, 3 incretin-based therapies are available and widely used in clinical practice. Several more agents are either under review by the Food and Drug Administration (FDA) or are in the very late stages of development. For diabetes educators trying to help their patients understand the differences among their antidiabetic medications, a comprehensive understanding of these agents and their role in therapy is imperative. (Source: The Diabetes Educator)
Source: The Diabetes Educator - September 24, 2009 Category: Endocrinology Authors: Campbell, R. K., Miller, S. Tags: Pharmacy Update Source Type: journals

Regulation of Na+/H+ Exchanger NHE3 by the Glucagon-Like Peptide 1 Receptor Agonist Exendin-4 in Renal Proximal Tubule Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The gut incretin hormone glucagon-like peptide 1 (GLP-1) is released in response to ingested nutrients and enhances insulin secretion. In addition to its insulinotropic properties, GLP-1 has been shown to have natriuretic actions paralleled by a diminished proton secretion. We therefore studied the role of the GLP-1 receptor agonist exendin-4 in modulating the activity of NHE3 in LLC-PK1 cells. We found that NHE3-mediated Na+-dependent intracellular pH recovery decreased approximately 50% after 30 minute-treatment with 1 nM exendin-4. Pharmacological inhibitors and cAMP analogs that selectively activate protein kinase ...
Source: American Journal of Physiology. Renal Physiology - September 22, 2009 Category: Physiology Authors: Carraro-Lacroix LR, Malnic G, Girardi AC Tags: Am J Physiol Renal Physiol Source Type: journals

Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects. PMID: 19776140 [PubMed - as supplied by publisher] (Source: The American Journal of Clinical Nutrition)
Source: The American Journal of Clinical Nutrition - September 22, 2009 Category: Nutrition Authors: Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De Backer F, Neyrinck AM, Delzenne NM Tags: Am J Clin Nutr Source Type: journals

New insights into the role of cAMP in the production and function of the incretin hormone glucagon-like peptide-1 (GLP-1).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The proglucagon gene (gcg) encodes both glucagon and glucagon-like pepetide-1 (GLP-1), produced in pancreatic alpha cells and intestinal endocrine L cells, respectively. The incretin hormone GLP-1 stimulates insulin secretion and pro-insulin gene transcription. GLP-1 also enhances pancreatic beta-cell proliferation, inhibits cell apoptosis, and has been utilized in the trans-differentiation of insulin producing cells. A long-term effective GLP-1 receptor agonist, Byetta, has now been developed as the drug in treating type II diabetes and potentially other metabolic disorders. The expression of gcg and the production of...
Source: Cellular Signalling - September 18, 2009 Category: Cytology Authors: Yu Z, Jin T Tags: Cell Signal Source Type: journals

Effects of the dipeptidyl peptidase-IV inhibitor ASP8497 on glucose tolerance in animal models of secondary failure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sulfonylureas promote insulin secretion and potently lower blood glucose levels, however, they induce hypoglycemia and undergo a reduction in efficacy when administered long-term (secondary failure). The dipeptidyl peptidase (DPP)-IV inhibitor ASP8497, (2S,4S)-4-fluoro-1-({[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile monofumarate, inhibits the degradation of glucagon-like peptide-1 (GLP-1), an incretin hormone, and promotes insulin secretion in a glucose-dependent manner. ASP8497 is therefore less likely to induce hypoglycemia and less likely to show reduced efficacy even after rep...
Source: European Journal of Pharmacology - September 15, 2009 Category: Drugs & Pharmacology Authors: Someya Y, Nakano R, Tahara A, Takasu T, Takeuchi A, Nagase I, Matsuyama-Yokono A, Hayakawa M, Sasamata M, Miyata K, Uchiyama Y Tags: Eur J Pharmacol Source Type: journals

Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions/interpretation Although the use of exendin-4 in rats is associated with decreased weight gain, lower insulin resistance and lower leptin levels than in control animals, extended use of exendin-4 in rats leads to pancreatic acinar inflammation and pyknosis. This raises important concerns about the likelihood of inducing acute pancreatitis in humans receiving incretin mimetic therapy. Content Type Journal ArticleCategory ArticleDOI 10.1007/s00125-009-1515-4Authors J. S. Nachnani, University of Missouri Kansas City Division of Gastroenterology and Hepatology 2411 Holmes Street Kansas City MO ...
Source: Diabetologia - September 15, 2009 Category: Endocrinology Tags: Diabetologia Source Type: journals

Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study is designed to determine the effects of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model of insulin resistance and insulin secretion defects. ICR mice were pre-treated with high fat diet and a low dose of streptozotocin to induce insulin resistance and impaired insulin secretion respectively. Diabetic mice were treated with sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon and improvement in oral glucose tolerance were observed in mice treated with sitagliptin. In contrast, g...
Source: European Journal of Pharmacology - September 14, 2009 Category: Drugs & Pharmacology Authors: Mu J, Petrov A, Eiermann GJ, Woods J, Zhou YP, Li Z, Zycband E, Feng Y, Zhu L, Roy RS, Howard AD, Li C, Thornberry NA, Zhang BB Tags: Eur J Pharmacol Source Type: journals

Design, statistical analysis and sample size calculation of a phase IIb/III study of linagliptin versus voglibose and placeboEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discussion: This is the first phase IIb/III study to examine the long-term safety and efficacy of linagliptin in diabetes patients in the Japanese population. Trial registration: Clinicaltrials.gov (NCT00654381). (Source: BioMed Central)
Source: BioMed Central - September 4, 2009 Category: Journals (General) Authors: Yoshiharu HorieNaoyuki HayashiKlaus DugiMasahiro Takeuchi Source Type: journals

TGR5-mediated bile acid sensing controls glucose homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show here that TGR5 signaling induces intestinal glucagon-like peptide-1 (GLP-1) release, leading to improved liver and pancreatic function and enhanced glucose tolerance in obese mice. In addition, we show that the induction of GLP-1 release in enteroendocrine cells by 6alpha-ethyl-23(S)-methyl-cholic acid (EMCA, INT-777), a sp...
Source: Cell Metabolism - August 31, 2009 Category: Cytology Authors: Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K Tags: Cell Metab Source Type: journals

Selecting among ADA/EASD tier 1 and tier 2 treatment options.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Each of the 4 groups of medications considered preferred therapies for treatment of T2DM by the ADA/EASD panel--insulin, sulfonylureas, TZDs, and incretin-based therapies (GLP-1 receptor agonists)--possesses significant advantages and disadvantages to be considered when individualizing treatment. Insulin and the sulfonylureas are the most researched therapies available, as well as the most cost-effective and the most effective in achieving glycemic goals. The TZDs have been shown to improve various markers of pancreatic beta-cell function; however, there is a risk of edema and heart failure with the TZDs; rosiglitazone...
Source: The Journal of Family Practice - August 31, 2009 Category: Practice Management Authors: McGill JB Tags: J Fam Pract Source Type: journals

Saxagliptin: a new option for the management of type 2 diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Incretin-based therapies for the treatment of diabetes mellitus (T2DM) present a new approach to disease management. Over recent years, several new drugs have entered the marketplace, and NICE have recently issued guidance on how best to incorporate these new drugs into treatment regimens. In this article, Marc Evans reviews saxagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, and considers its potential clinical use. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Future Prescriber)
Source: Future Prescriber - August 12, 2009 Category: Drugs & Pharmacology Authors: Marc Evans Tags: Drug Profiles Source Type: journals

Glucose, Metformin, and AICAR Regulate the Expression of G Protein-coupled Receptor Members in INS-1 β CellEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Horm Metab ResDOI: 10.1055/s-0029-1234043AbstractGlucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family. They are abundantly expressed in islet β cells, and mediate effects of incretins and fatty acids in β cells. Glucose and 5-AMP-activated protein kinase (AMPK) are known to be involved in the regulation of β cell function. Metformin and the potential therapeutic drug for type 2 diabetes, 5-amino-4-imidazolecarboxamide riboside (AICAR), are both known activator...
Source: Hormone and Metabolic Research - August 12, 2009 Category: Endocrinology Tags: Original Basic Source Type: journals

Gut chemosensing: Interactions between gut endocrine cells and visceral afferents.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, ...
Source: Autonomic Neuroscience - August 9, 2009 Category: Neuroscience Authors: Raybould HE Tags: Auton Neurosci Source Type: journals

PrefaceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This issue of Best Practice & Research Clinical Endocrinology & Metabolism is entirely devoted to the subjects of incretin hormones and their therapeutic potential in patients with type 2 diabetes. The development of incretin-based antidiabetic medications is a story of success originating from academic institutions and their interest in physiological mechanisms regulating insulin secretion after meals. Obviously, any gut-derived hormone with the ability to potently augment glucose-induced insulin secretion (this is the definition of an incretin hormone) should have therapeutic potential. However, the first incretin hormon...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Michael A. Nauck Source Type: journals

Immunoassays for the incretin hormones GIP and GLP-1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The measurement of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), using immunologically based assays is made difficult by the fact that the processing of the precursor molecules gives rise to a number of different peptides which cross-react with antisera raised against the two hormones. For GLP-1, the picture is further complicated because of the necessity to differentiate between the intestinal and pancreatic proglucagon products. Finally, once secreted, both incretins are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) to generate metabolites w...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Carolyn F. Deacon, Jens J. Holst Source Type: journals

The contribution of incretin hormones to the pathogenesis of type 2 diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article will describe the defects in the incretin system in patients with type 2 diabetes, summarise their relevance in the development of hyperglycaemia and discuss the potential individual roles of GIP and GLP-1 in the pathogenesis of type 2 diabetes. (Source: Best Practice & Research. Clinical Endocrinology & Metabolism)
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Juris J. Meier Source Type: journals

Mechanisms underlying the rapid degradation and elimination of the incretin hormones GLP-1 and GIPEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, gastric inhibitory peptide) are secreted from intestinal L and K cells and stimulate insulin secretion from pancreatic beta cells. However, they are immediately inactivated mainly via N-terminal degradation by dipeptidyl peptidase IV (DPP IV, CD26), a specialised enzyme located on the cell surface enzyme of endothelial, epithelial and some other cell types. Cleavage by neprilysin (neutral endopeptidase) is a minor degradation route, and renal clearance eliminates incretin/fragments, but appears of less importance for re...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Rolf Mentlein Source Type: journals

The spectrum of antidiabetic actions of GLP-1 in patients with diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article focusses on the antidiabetic therapeutic potential of the incretin hormone glucagon-like peptide-1 (GLP-1) in the treatment of patients with type 2 diabetes mellitus (T2DM). T2DM is characterised by insulin resistance, impaired glucose-induced insulin secretion and inappropriately regulated glucagon secretion, which in combination eventually result in hyperglycaemia and, in the longer term, microvascular and macrovascular diabetic complications. Traditional treatment modalities – even multidrug approaches – for T2DM are often unsatisfactory in making patients reach glycaemic goals as the disease progresses...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Tina Vilsbøll, Jens J. Holst, Filip K. Knop Source Type: journals

Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics) – preclinical and clinical resultsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The GLP-1 analogues exenatide and liraglutide stimulate insulin secretion and inhibit glucagon output in a glucose-dependent manner, slow gastric emptying and decrease appetite. The injectable glucagon-like peptide-1 (GLP-1) receptor agonist exenatide significantly improves glycaemic control, with average reductions in HbA1c of about 1.0% point, fasting plasma glucose of about 1.4mmoll−1, and causes a weight loss of approximately 2–3kg after 30 weeks of treatment. The adverse effects are transient nausea and vomiting. The long-acting once-daily human GLP-1 receptor agonist liraglutide reduces HbA1c by about 1.0–2.0% ...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: Sten Madsbad Source Type: journals

Incretin-based therapy: how do incretin mimetics and DPP-4 inhibitors fit into treatment algorithms for type 2 diabetic patients?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Incretin-based antidiabetic medications have been approved for clinical use for approximately two to three years. While their major clinical characteristics have been known from clinical trials, the discussion now focuses on the best clinical use of GLP-1 receptor agonists (incretin mimetics) and inhibitors of the protease dipeptidyl peptidase-4 (DPP-4). Any novel drug will not fully disclose its spectrum of beneficial and adverse activity before long-term trials with clinical endpoints are available. This, typically, will last 5-8 years. Nevertheless, there are convincing reasons to use incretin mimetics and DPP-4 inhibit...
Source: Best Practice & Research. Clinical Endocrinology & Metabolism - July 31, 2009 Category: Endocrinology Authors: M. Nauck, U. Smith Source Type: journals

T1r3 and α-Gustducin in Gut Regulate Secretion of Glucagon-like Peptide-1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that underlies the augmented insulin release from the pancreas in response to glucose in the gut lumen more than to intravenous injected glucose (the "incretin effect"). GLP-1, found in enteroendocrine L cells of the gut, regulates appetite and gut motility and is released from L cells in response to glucose. GLP-1-expressing duodenal L cells also express T1r taste receptors, [alpha]-gustducin, and many other taste transduction elements. Knockout mice lacking [alpha]-gustducin or T1r3 have deficiencies in secretion of GLP-1 and in the regulation of plasma levels of ins...
Source: Annals of the New York Academy of Sciences - July 28, 2009 Category: Science Authors: Zaza Kokrashvili, Bedrich Mosinger, Robert F. Margolskee Tags: Part I. Peripheral Events in Chemosensory Systems Source Type: journals

Liraglutide: A Once-Daily Incretin Mimetic for the Treatment of Type 2 Diabetes Mellitus (September)(CE).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: Once-daily administration may provide a therapeutic advantage for liraglutide over twice-daily exenatide, with similar improvements in A1C and body weight observed when liraglutide was compared with exenatide. The glucose-dependent mechanism of insulin release with GLP-1 agonist therapy holds potential clinical significance in the management of postprandial hyperglycemic excursions, with minimal risk of hypoglycemia. PMID: 19638470 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)
Source: The Annals of Pharmacotherapy - July 27, 2009 Category: Drugs & Pharmacology Authors: Neumiller JJ, Campbell RK Tags: Ann Pharmacother Source Type: journals

Stimulation of incretin secretion by dietary lipid: is it dose dependent?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
After the ingestion of nutrients, secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the enteroendocrine cells increases rapidly. Previous studies have shown that oral ingestion of fat stimulates secretion of both incretins; however, it is unclear whether there is a dose-dependent relationship between the amount of lipid ingested and the secretion of the hormones in vivo. Recently, we found a higher concentration of the incretin hormones in intestinal lymph than in peripheral or portal plasma. We therefore used the lymph fistula rat model to test for...
Source: AJP: Gastrointestinal and Liver Physiology - July 20, 2009 Category: Gastroenterology Authors: Yoder, S. M., Yang, Q., Kindel, T. L., Tso, P. Tags: HORMONES AND SIGNALING Source Type: journals

A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patie...
Source: Cardiovascular Diabetology - July 19, 2009 Category: Cardiology Authors: Enrique FismanAlexander Tenenbaum Source Type: journals

Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgeryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions: We conclude that at 1 year after bariatric surgery, the two incretins show dissociated responses in that the GIP secretion is higher after VBG whereas GLP-1 secretion is higher after JIB. This dissociated incretin response is independent from reduction in body weight, glucose tolerance or insulin secretion. (Source: Diabetes, Obesity and Metabolism)
Source: Diabetes, Obesity and Metabolism - July 12, 2009 Category: Endocrinology Authors: M. Guldstrand, B. Ahrén, E. Näslund, J. J. Holst, U. Adamson Source Type: journals

Mining incretin hormone pathways for novel therapies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are produced predominantly by enteroendocrine cells and have multiple blood glucose-lowering effects. Recent years have seen a surge of interest in understanding the basic physiology and pathophysiology of incretins and in applying this knowledge to the treatment of diabetes and obesity. Considerable gains have been made in elucidating the mechanisms controlling incretin secretion, and there is growing evidence to suggest that incretins might be involved in the rapid reversal of diabetes observed in gastric by...
Source: Trends in Endocrinology and Metabolism: TEM - July 9, 2009 Category: Endocrinology Authors: Wideman RD, Kieffer TJ Tags: Trends Endocrinol Metab Source Type: journals

WNT/β-catenin increases the production of incretins by entero-endocrine cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions/interpretation Lithium and WNT are incretin inducers in general. This work provides a novel link between WNT signalling, obesity and diabetes. Content Type Journal ArticleCategory ArticleDOI 10.1007/s00125-009-1429-1Authors J. M. García-Martínez, Universidad Rey Juan Carlos Dptal I. Despacho 020, Facultad de Ciencias de la Salud 28922 Alcorcon Madrid SpainA. Chocarro-Calvo, Universidad Rey Juan Carlos Dptal I. Despacho 020, Facultad de Ciencias de la Salud 28922 Alcorcon Madrid SpainC. M. Moya, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC...
Source: Diabetologia - July 7, 2009 Category: Endocrinology Tags: Diabetologia Source Type: journals

Treatment options for type 2 diabetes:introducing the incretin-based therapiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In type 2 diabetes mellitus (T2DM), glycaemic control is often difficult to maintain and current treatments can produce adverse effects. The incretin-based therapies - dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) agonists - improve glycaemic control when added to conventional therapies and are well tolerated, with a low incidence of hypoglycaemia. In addition, the GLP-1 agonists reduce body weight and systolic blood pressure and improve surrogates of [beta]-cell function. Incretin-based therapies may be appropriate for selected patients with T2DM when first-line therapy does not maintain glycaemic ...
Source: Practical Diabetes International - July 5, 2009 Category: Endocrinology Authors: AH Barnett Tags: Reviews Source Type: journals

The role of incretin-based therapies in the management of type 2 diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In patients with type 2 diabetes mellitus (T2DM), goals for blood glucose and other cardiovascular risk factors, such as blood pressure and body weight, can be difficult to achieve. Recent clinical trials indicate that incretin-based therapies - dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) agonists - help to achieve glycaemic goals and are generally well tolerated, with a low prevalence of hypoglycaemia. GLP-1 agonists also improve weight, blood pressure and markers of [beta]-cell function. Addition of an incretin-based agent may be appropriate for selected patients with T2DM and unsatisfactory gly...
Source: Practical Diabetes International - July 5, 2009 Category: Endocrinology Authors: D Russell-Jones Tags: Reviews Source Type: journals

ABCD position statement on incretin mimetics and DPP-4 inhibitors -2009Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Association of British Clinical Diabetologists (ABCD) currently recommends a limited place for exenatide and the gliptins in obese type 2 diabetes. Exenatide requires careful patient selection and continued specialist support, particularly to avoid initiation in individuals at risk of pancreatitis or for those who are already on insulin therapy. Hypoglycaemic and weight reduction efficacy may vary depending on baseline levels of HbA1c and body mass index. Continuation of therapy beyond six months should be determined by changes in weight and/or HbA1c. Gliptins should be reserved for less obese, less hyperglycaemic case...
Source: Practical Diabetes International - July 5, 2009 Category: Endocrinology Authors: CMB Edwards, PH Winocour, on behalf of the Association of British Clinical Diabetologists (ABCD) Tags: Position Statements Source Type: journals

Incretins In The ICU: Is Insulin On Its Way Out?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Incretin such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients. Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in lager studies. Potential limitations include the need for a continuou...
Source: Critical Care - July 1, 2009 Category: Intensive Care Authors: Michelle KovalaskeGunjan Gandhi Source Type: journals

Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many of the receptors and downstream signaling elements involved in taste detection and transduction are also expressed in enteroendocrine cells where they underlie the chemosensory functions of the gut. In one well-known example of gastrointestinal chemosensation (the "incretin effect"), it is known that glucose that is given orally, but not systemically, induces secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide (the incretin hormones), which in turn regulate appetite, insulin secretion, and gut motility. Duodenal L cells express sweet taste receptors, the taste G protein gustducin, and...
Source: The American Journal of Clinical Nutrition - June 30, 2009 Category: Nutrition Authors: Kokrashvili Z, Mosinger B, Margolskee RF Tags: Am J Clin Nutr Source Type: journals

Intracerebroventricular infusion of bombesin modulates GIP secretion in conscious dogs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: Intracerebroventricular levels of bombesin seems to involve in the neural regulation of GIP secretion independently of the presence of nutrients and to potentiate GIP secretion during a glucose load. PMID: 19576914 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 30, 2009 Category: Drugs & Pharmacology Authors: Yavropoulou MP, Kotsa K, Anastasiou OE, O'Dorisio TM, Pappas TN, Yovos JG Tags: Neuropharmacology Source Type: journals

Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article examines clinical trial data and accepted algorithms with a view toward elucidating the application of these agents in routine clinical practice. We propose a systematic approach to treatment, addressing (1) patient selection, (2) optimal treatment combinations, and (3) timing and guidance for both initiation and intensification of therapy. The GLP-1 receptor agonists, for example, could be particularly beneficial in patients whose weight significantly increases cardiovascular risk. Early use of these agents may be effective in preventing diabetes in those at risk, or in halting or retarding disease progressio...
Source: European Journal of Internal Medicine - June 30, 2009 Category: Internal Medicine Authors: Kendall DM, Cuddihy RM, Bergenstal RM Tags: Eur J Intern Med Source Type: journals

Incretin therapies: effects beyond glycemic control.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Impaired insulin secretion plays a major role in the pathogenesis of type 2 diabetes mellitus, and progressive loss of beta-cell function is a pathophysiologic hallmark of type 2 diabetes. Recent science has elaborated on the role of the incretin hormones on beta-cell function and insulin secretion, as well as the role that incretin-based pharmacotherapies may have on glycemic control and beta-cell function, possibly altering the progressive loss of beta-cell function and possibly reversing/halting disease progression. However, incretin-based therapies may also have benefits extending beyond glycemic control and insuli...
Source: European Journal of Internal Medicine - June 30, 2009 Category: Internal Medicine Authors: Mudaliar S, Henry RR Tags: Eur J Intern Med Source Type: journals

Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. PMID: 1958...
Source: European Journal of Internal Medicine - June 30, 2009 Category: Internal Medicine Authors: Gilbert MP, Pratley RE Tags: Eur J Intern Med Source Type: journals

Unraveling the science of incretin biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 2 diabetes mellitus has become an enormous and worldwide healthcare problem that is almost certain to worsen. Current therapies, which address glycemia and insulin resistance, have not adequately addressed the complications and treatment failures associated with this disease. New treatments based on the incretin hormones provide a novel approach to address some components of the complex pathophysiology of type 2 diabetes. The purpose of this review is to elucidate the science of the incretin hormones and describe the incretin effect and its regulatory role in beta-cell function, insulin secretion, and glucose meta...
Source: European Journal of Internal Medicine - June 30, 2009 Category: Internal Medicine Authors: Nauck MA Tags: Eur J Intern Med Source Type: journals