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- Title
Glucagon-Like Peptide-1: Regulation of Insulin Secretion and Therapeutic Potential.
- Authors
Gromada, Jesper; Brock, Birgitte; Schmitz, Ole; Rorsman, Patrik
- Abstract
Glucagon-like peptide-1 (GLP-1) is an intestinally derived insulinotropic hormone currently under investigation for use as a novel therapeutic agent in the treatment of type 2 diabetes. One of several important effects of GLP-1 is on nutrient-induced pancreatic hormone release and is mediated by binding to a specific G-protein coupled receptor resulting in the activation of adenylate cyclase and an increase in cAMP generation. In theβ-cell, cAMP binds and modulates activities of both protein kinase A and cAMP-regulated guanine nucleotide exchange factor II, thereby enhancing glucose-dependent insulin secretion. The stimulatory action of GLP-1 on insulin secretion involves interaction with a plethora of signal transduction processes including ion channel activity, intracellular Ca2+ handling and exocytosis of the insulin-containing granules. In this review we focus principally on recent advances in our understanding on the cellular mechanisms proposed to underlie GLP-1's insulinotropic effect and attempt to incorporate this knowledge into a working model for the control of insulin secretion. Lastly, this review discusses the applicability of GLP-1 as a therapeutic agent for the treatment of type 2 diabetes.
- Subjects
UNITED States; GLUCAGON-like peptide 1; GASTROINTESTINAL hormones; PEPTIDE hormones; TYPE 2 diabetes; DIABETES; PHARMACOLOGY; MEDICAL sciences
- Publication
Basic & Clinical Pharmacology & Toxicology, 2004, Vol 95, Issue 6, p252
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/j.1742-7843.2004.t01-1-pto950502.x