Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7–37) or the related GLP-I(7–36)amide. These hormones have specific β-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep β-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the β-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.
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Perspectives in Diabetes| September 01 1993
Glucagon-Like Peptide-I and the Control of Insulin Secretion in the Normal State and in NIDDM
Address correspondence and reprint requests to Dr. Bernard Thorens, Institute of Pharmacology and Toxicology, Bugnon 27, 1005 Lausanne, Switzerland.
Bernard Thorens, Gerard Waeber; Glucagon-Like Peptide-I and the Control of Insulin Secretion in the Normal State and in NIDDM. Diabetes 1 September 1993; 42 (9): 1219–1225. https://doi.org/10.2337/diab.42.9.1219
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