Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM.

Abstract

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 beta-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 beta-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 beta-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.

• Authors: B Thorens, G Waeber
• Journal: Diabetes (Diabetes) Vol. 42 Issue 9 Pg. 1219-25 (Sep 1993) ISSN: 0012-1797 [Print] United States
• PMID: 8349031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Insulin
• Peptide Fragments
• Peptides
• Protein Precursors
• glucagon-like peptide 1 (7-36)amide
• Glucagon-Like Peptides
• Glucagon-Like Peptide 1
• Glucagon

Topics

• Animals
• Cloning, Molecular
• Diabetes Mellitus, Type 2 (drug therapy, physiopathology)
• Glucagon (physiology, therapeutic use)
• Glucagon-Like Peptide 1
• Glucagon-Like Peptides
• Humans
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (physiology)
• Peptide Fragments (physiology, therapeutic use)
• Peptides (physiology, therapeutic use)
• Protein Precursors (physiology, therapeutic use)
• Signal Transduction (physiology)