Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro- duodenal motility in humans

Schirra, J.; Nicolaus, M.; Roggel, R.; Katschinski, M.; Storr, M.; Woerle, H. J.; Göke, B.
February 2006
Gut;Feb2006, Vol. 55 Issue 2, p243
Academic Journal
Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1 ) lowers glycaemia by stimulation of insulin, inhibition of glucogon, and deice, of gastric emptying. Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloroduodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2). Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9–39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenel glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloroduodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments. Results: Ex(9–39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9–39)NH2 raised plasma glucogon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9–39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation. Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic α cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogostrone in humans.


Related Articles

  • Vasoactive Intestinal Peptide--Null Mice Demonstrate Enhanced Sweet Taste Preference, Dysglycemia, and Reduced Taste Bud Leptin Receptor Expression. Martin, Bronwen; Yu-Kyong Shin; White, Caitlin M.; Sunggoan Ji; Wook Kim; Carlson, Olga D.; Napora, Joshua K.; Chadwick, Wayne; Chapter, Megan; Waschek, James A.; Mattson, Mark P.; Maudsley, Stuart; Egan, Josephine M. // Diabetes;May2010, Vol. 59 Issue 5, p1143 

    OBJECTIVE--It is becoming apparent that there is a strong link between taste perception and energy homeostasis. Recent evidence implicates gut-related hormones in taste perception, including glucagon-like peptide 1 and vasoactive intestinal peptide (VIP). We used VIP knockout mice to investigate...

  • To be or not to be-an incretin or enterogastrone? Horowitz, M.; Nauck, M. A. // Gut;Feb2006, Vol. 55 Issue 2, p148 

    Glucagon-like peptide 1 does not comfortably fulfil the criterion of a gut derived factor responsible for an enhanced meal related insulin response; it appears logical to add the definition of a ‘physiological incretin hormone’.

  • Reversal of Obesity and Insulin Resistance by a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist in Diet-Induced Obese Mice. Min He; Haoran Su; Weiwei Gao; Johansson, Stina M.; Qing Liu; Xiaoyan Wu; Jiayu Liao; Young, Andrew A.; Tamas Bartfai; Ming-Wei Wang // PLoS ONE;2010, Vol. 5 Issue 12, p1 

    Background: Glucagon-like peptide-1 (GLP-1) is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a...

  • Glucagon-Like Peptide-1 Receptor Signaling in the Lateral Parabrachial Nucleus Contributes to the Control of Food Intake and Motivation to Feed. Alhadeff, Amber L; Baird, John-Paul; Swick, Jennifer C; Hayes, Matthew R; Grill, Harvey J // Neuropsychopharmacology;Aug2014, Vol. 39 Issue 9, p2233 

    Central glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and the motivation to work for food, but the neurons and circuits mediating these effects are not fully understood. Although lateral parabrachial nucleus (lPBN) neurons are implicated in the control of food intake...

  • Incretin hormones in the treatment of type 2 diabetes. Trujillo, Jennifer // Formulary;Mar2006, Vol. 41 Issue 3, p130 

    Type 2 diabetes mellitus is a progressive disease affecting more than 18 million Americans, lncretin mimetics and DPP-IV inhibitors are new classes of antihyperglycemic agents that may improve glycemic control in patients with type 2 diabetes. The incretin hormone, glucagon-like peptide 1...

  • Enhancing Central Nervous System Endogenous GLP-1 Receptor Pathways for Intervention in Alzheimer's Disease. Perry, TracyAnn; Greig, Nigel H. // Current Alzheimer Research;Jul2005, Vol. 2 Issue 3, p377 

    Glucagon - like peptide - 1 (7-36) - amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the gastrointestinal tract in response to food. It enhances pancreatic islet �-cell proliferation, glucose-dependent insulin secretion, and lowers blood glucose and food intake...

  • Comparative Effects of the Long-Acting GLP-1 Receptor Ligands, Liraglutide and Exendin-4, on Food Intake and Body Weight Suppression in Rats. Hayes, Matthew R.; Kanoski, Scott E.; Alhadeff, Amber L.; Grill, Harvey J. // Obesity (19307381);Jul2011, Vol. 19 Issue 7, p1342 

    The glucagon-like-peptide-1 receptor (GLP-1R) agonists, liraglutide (Victoza) and the synthetic product of exendin-4 (Byetta), are approved for type II diabetes mellitus (T2DM) treatment and may be efficacious in obesity treatment as well, in part, due to the drugs' resistance to enzymatic...

  • Liraglutide: Promise of the Incretin Class.  // Neurology Alert;Mar2009 Clinical Briefs in Pr, Vol. 14 Issue 3, p5 

    The article discusses a study made on liraglutide (LIR), a synthetic glucagon-like peptide-1 with a half-life of 13 hours allowing once-daily dosing. It references a study made by M. Nauck, et al published in "Diabetes Care." The study found that test subjects has a one percent blood sugar...

  • Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Brubaker, Patricia L.; Anini, Younes // Canadian Journal of Physiology & Pharmacology;Nov2003, Vol. 81 Issue 11, p1005 

    The proglucagon-derived peptide family consists of three highly related peptides, glucagon and the glucagon-like peptides GLP-1 and GLP-2. Although the biological activity of glucagon as a counter-regulatory hormone has been known for almost a century, studies conducted over the past decade have...


Read the Article


Sign out of this library

Other Topics