|
|
||||||||
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.
This article has been cited by other articles:
![]() |
E. Christ, D. Wild, F. Forrer, M. Brandle, R. Sahli, T. Clerici, B. Gloor, F. Martius, H. Maecke, and J. C. Reubi Glucagon-Like Peptide-1 Receptor Imaging for Localization of Insulinomas J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4398 - 4405. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Al-Trad, K. Reisberg, T. Wittek, G. B. Penner, A. Alkaassem, G. Gabel, M. Furll, and J. R. Aschenbach Increasing intravenous infusions of glucose improve body condition but not lactation performance in midlactation dairy cows J Dairy Sci, November 1, 2009; 92(11): 5645 - 5658. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Holmes, K. N. Browning, M. Tong, E. Qualls-Creekmore, and R. A. Travagli Vagally mediated effects of glucagon-like peptide 1: in vitro and in vivo gastric actions J. Physiol., October 1, 2009; 587(19): 4749 - 4759. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Misler Unifying concepts in stimulus-secretion coupling in endocrine cells and some implications for therapeutics Advan Physiol Educ, September 1, 2009; 33(3): 175 - 186. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Williams Minireview: Finding the Sweet Spot: Peripheral Versus Central Glucagon-Like Peptide 1 Action in Feeding and Glucose Homeostasis Endocrinology, July 1, 2009; 150(7): 2997 - 3001. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Zinman, J. Gerich, J. B. Buse, A. Lewin, S. Schwartz, P. Raskin, P. M. Hale, M. Zdravkovic, L. Blonde, and the LEAD-4 Study Investigators Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD) Diabetes Care, July 1, 2009; 32(7): 1224 - 1230. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Abu-Hamdah, A. Rabiee, G. S. Meneilly, R. P. Shannon, D. K. Andersen, and D. Elahi The Extrapancreatic Effects of Glucagon-Like Peptide-1 and Related Peptides J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 1843 - 1852. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Chen, S. L. Lee, and R. A. Peterfreund New Therapeutic Agents for Diabetes Mellitus: Implications for Anesthetic Management Anesth. Analg., June 1, 2009; 108(6): 1803 - 1810. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-y. Ueda, T. Yoshikawa, Y. Katsura, T. Usui, H. Nakao, and S. Fujimoto Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males J. Endocrinol., April 1, 2009; 201(1): 151 - 159. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Vollmer, H. Gardiwal, B. A. Menge, O. Goetze, C. F. Deacon, W. E. Schmidt, J. J. Holst, and J. J. Meier Hyperglycemia Acutely Lowers the Postprandial Excursions of Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide in Humans J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1379 - 1385. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Ferrannini and G. Mingrone Impact of Different Bariatric Surgical Procedures on Insulin Action and {beta}-Cell Function in Type 2 Diabetes Diabetes Care, March 1, 2009; 32(3): 514 - 520. [Full Text] [PDF] |
||||
![]() |
J. Vidal, J. Nicolau, F. Romero, R. Casamitjana, D. Momblan, I. Conget, R. Morinigo, and A. M. Lacy Long-Term Effects of Roux-en-Y Gastric Bypass Surgery on Plasma Glucagon-Like Peptide-1 and Islet Function in Morbidly Obese Subjects J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 884 - 891. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. B. Ruttimann, M. Arnold, J. J. Hillebrand, N. Geary, and W. Langhans Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms Endocrinology, March 1, 2009; 150(3): 1174 - 1181. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Y. Enc, T. Ones, H. L. Akin, F. Dede, H. T. Turoglu, G. Ulfer, N. Bekiroglu, G. Haklar, J. F. Rehfeld, J. J. Holst, et al. Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G482 - G489. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Rosker, G. Meur, E. J. A. Taylor, and C. W. Taylor Functional Ryanodine Receptors in the Plasma Membrane of RINm5F Pancreatic {beta}-Cells J. Biol. Chem., February 20, 2009; 284(8): 5186 - 5194. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. G. Webb, R. Williams, and M. S. Marber Lizard spit and reperfusion injury. J. Am. Coll. Cardiol., February 10, 2009; 53(6): 511 - 513. [Full Text] [PDF] |
||||
![]() |
F. Zhang, D. Dey, R. Branstrom, L. Forsberg, M. Lu, Q. Zhang, and A. Sjoholm BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP-activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose-stimulated insulin secretion in a PI3K-dependent manner Am J Physiol Cell Physiol, February 1, 2009; 296(2): C346 - C354. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Vetter, S. Cardillo, M. R. Rickels, and N. Iqbal Narrative Review: Effect of Bariatric Surgery on Type 2 Diabetes Mellitus Ann Intern Med, January 20, 2009; 150(2): 94 - 103. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nauck, A. Frid, K. Hermansen, N. S. Shah, T. Tankova, I. H. Mitha, M. Zdravkovic, M. During, D. R. Matthews, and for the LEAD-2 Study Group Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes: The LEAD (Liraglutide Effect and Action in Diabetes)-2 study Diabetes Care, January 1, 2009; 32(1): 84 - 90. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Tolhurst, F. Reimann, and F. M. Gribble Nutritional regulation of glucagon-like peptide-1 secretion J. Physiol., January 1, 2009; 587(1): 27 - 32. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Asarian Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2009; 296(1): R51 - R56. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Wang, Y. Wang, X. Li, J. Li, and F. C. Leung Cloning, Tissue Distribution, and Functional Characterization of Chicken Glucagon Receptor Poult. Sci., December 1, 2008; 87(12): 2678 - 2688. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Kim and J. M. Egan The Role of Incretins in Glucose Homeostasis and Diabetes Treatment Pharmacol. Rev., December 1, 2008; 60(4): 470 - 512. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Holst Pharmacology of GLP-1-based therapies The British Journal of Diabetes & Vascular Disease, November 1, 2008; 8(2_suppl): S10 - S18. [Abstract] [PDF] |
||||
![]() |
C. Knauf, P. D. Cani, D.-H. Kim, M. A. Iglesias, C. Chabo, A. Waget, A. Colom, S. Rastrelli, N. M. Delzenne, D. J. Drucker, et al. Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing Diabetes, October 1, 2008; 57(10): 2603 - 2612. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Cabou, G. Campistron, N. Marsollier, C. Leloup, C. Cruciani-Guglielmacci, L. Penicaud, D. J. Drucker, C. Magnan, and R. Burcelin Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity Diabetes, October 1, 2008; 57(10): 2577 - 2587. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Hausenloy and D. M. Yellon GLP-1 Therapy: Beyond Glucose Control Circ Heart Fail, September 1, 2008; 1(3): 147 - 149. [Full Text] [PDF] |
||||
![]() |
D. Tornehave, P. Kristensen, J. Romer, L. B. Knudsen, and R. S. Heller Expression of the GLP-1 Receptor in Mouse, Rat, and Human Pancreas J. Histochem. Cytochem., September 1, 2008; 56(9): 841 - 851. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Laferrere, J. Teixeira, J. McGinty, H. Tran, J. R. Egger, A. Colarusso, B. Kovack, B. Bawa, N. Koshy, H. Lee, et al. Effect of Weight Loss by Gastric Bypass Surgery Versus Hypocaloric Diet on Glucose and Incretin Levels in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2479 - 2485. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Begriche, P. Letteron, A. Abbey-Toby, N. Vadrot, M.-A. Robin, A. Bado, D. Pessayre, and B. Fromenty Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E939 - E951. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |