Glucagon‐like peptide‐1 (GLP‐1): A gut hormone of potential interest in the treatment of diabetes

GLP‐1 (glucagon‐like peptide‐1) is a gut hormone which is released into the blood stream after feeding. Its main action is to stimulate insulin secretion through potentiating the insulinotropic action of glucose. The peptide is encoded in the glucagon gene and expressed mainly in the gut L cells. It exerts its actions through activating specific receptors of the seven transmembraneous domain‐G‐protein‐coupled type with 463 amino acids. Its main signalling mechanism is activation of adenylate cyclase and formation of cyclic AMP. The peptide also increases the cytoplasmic concentration of Ca2 which is thought to be executed both through a Na+‐dependent uptake of extracellular Ca2+ and through release of Ca2+ from intracellular Ca2+ stores. GLP‐1 also inhibits glucagon secretion and inhibits gastric emptying and gastric acid and pancreatic exocrine secretion. Its integrated action on carbohydrate metabolism results in reduction of circulating glucose, and GLP‐1 has therefore been suggested as a therapeutic alternative in diabetes. Finally, GLP‐1 is also expressed in neurons in the hypothalamus, and may be involved in the regulation of feeding behaviour, since it inhibits food intake. BioEssays 20:642–651, 1998.© 1998 John Wiley & Sons Inc.

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