Insulin secretion is controlled by a complex set of factors that include not only glucose but amino acids, catecholamines, and intestinal hormones. We report that a novel glucagon-like peptide, co-encoded with glucagon in the glucagon gene is a potent insulinotropic factor. The glucagon gene encodes a proglucagon that contains in its sequence glucagon and additional glucagon-like peptides (GLPs). These GLPs are liberated from proglucagon in both the pancreas and intestines. GLP-I exists in at least two forms: 37 amino acids GLP-I(1-37), and 31 amino acids, GLP-I(7-37). We studied the effects of synthetic GLP-Is on insulin secretion in the isolated perfused rat pancreas. In the presence of 6.6 mM glucose, GLP-I(7-37) is a potent stimulator of insulin secretion at concentrations as low as 5 X 10(-11) M (3- to 10-fold increases over basal). GLP-I(1-37) had no effect on insulin secretion even at concentrations as high as 5 X 10(-7) M. The earlier demonstration of specific liberation of GLP-I(7-37) in the intestine and pancreas, and the magnitude of the insulinotropic effect at such low concentrations, suggest that GLP-I(7-37) participates in the physiological regulation of insulin secretion. Images
Svetlana Mojsov, Gordon C. Weir, Joel F. Habener
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Title and authors | Publication | Year |
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Gastrointestinal hormones regulating appetite
O Chaudhri, C Small, S Bloom |
Philosophical Transactions of the Royal Society B: Biological Sciences | 2006 |
Major contributions of comparative endocrinology to the development and exploitation of the incretin concept
JM Conlon, S Patterson, PR Flatt |
Journal of Experimental Zoology Part A: Comparative Experimental Biology | 2006 |
Gut?Brain Axis: Regulation of Glucose Metabolism
AC Heijboer, H Pijl, AM van Hoek, LM Havekes, JA Romijn, EP Corssmit |
Journal of Neuroendocrinology | 2006 |
Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005
JJ Holst |
Diabetologia | 2006 |
Glucagon-Like Peptide-2: Update of the Recent Clinical Trials
PB Jeppesen |
Gastroenterology | 2006 |
Newer therapeutic options for children with diabetes mellitus: theoretical and practical considerations
GS Jeha, RA Heptulla |
Pediatric Diabetes | 2006 |
Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures
CM Mack, CX Moore, CM Jodka, S Bhavsar, JK Wilson, JA Hoyt, JL Roan, C Vu, KD Laugero, DG Parkes, AA Young |
International Journal of Obesity | 2006 |
“The next big thing” in diabetes: clinical progress on DPP-IV inhibitors
TW von Geldern, JM Trevillyan |
Drug Development Research | 2006 |
Increased insulin resistance and β cell activity in patients with Crohn's disease
N Bregenzer, A Hartmann, U Strauch, J Schölmerich, T Andus, LC Bollheimer |
Inflammatory Bowel Diseases | 2006 |
Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1)
RD Wideman, IL Yu, TD Webber, CB Verchere, JD Johnson, AT Cheung, TJ Kieffer |
Proceedings of the National Academy of Sciences | 2006 |
GLP-1 based therapy for type 2 diabetes
DK Arulmozhi, B Portha |
European Journal of Pharmaceutical Sciences | 2006 |
Using Evolutionary Information and Ancestral Sequences to Understand the Sequence–Function Relationship in GLP-1 Agonists
M Skovgaard, JT Kodra, DX Gram, SM Knudsen, D Madsen, DA Liberles |
Journal of Molecular Biology | 2006 |
Free fatty acids administered into the colon promote the secretion of glucagon-like peptide-1 and insulin
T Adachi, T Tanaka, K Takemoto, T Koshimizu, A Hirasawa, G Tsujimoto |
Biochemical and Biophysical Research Communications | 2006 |
Liraglutide, a Long-Acting Glucagon-Like Peptide-1 Analog, Reduces Body Weight and Food Intake in Obese Candy-Fed Rats, Whereas a Dipeptidyl Peptidase-IV Inhibitor, Vildagliptin, Does Not
K Raun, P Voss, CF Gotfredsen, V Golozoubova, B Rolin, LB Knudsen |
Diabetes | 2006 |
Pancreatic and Extrapancreatic Effects of Gastric Inhibitory Polypeptide
Y Yamada, K Miyawaki, K Tsukiyama, N Harada, C Yamada, Y Seino |
Diabetes | 2006 |
Physiology of the Gastrointestinal Tract
DJ Drucker |
Physiology of the Gastrointestinal Tract | 2006 |
Exogenously imposed postprandial-like rises in systemic glucose and GLP-1 do not produce an incretin effect, suggesting an indirect mechanism of GLP-1 action
V Ionut, IF Liberty, K Hucking, M Lottati, D Stefanovski, D Zheng, RN Bergman |
American journal of physiology. Endocrinology and metabolism | 2006 |
Discovery, Structure−Activity Relationship, and Pharmacological Evaluation of (5-Substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as Potent Dipeptidyl Peptidase IV Inhibitors
Z Pei, X Li, K Longenecker, TW von Geldern, PE Wiedeman, TH Lubben, BA Zinker, K Stewart, SJ Ballaron, MA Stashko, AK Mika, DW Beno, M Long, H Wells, AJ Kempf-Grote, DJ Madar, TS McDermott, L Bhagavatula, MG Fickes, D Pireh, LR Solomon, MR Lake, R Edalji, EH Fry, HL Sham, JM Trevillyan |
Journal of Medicinal Chemistry | 2006 |