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Horm Metab Res 2004; 36(11/12): 822-829
DOI: 10.1055/s-2004-826169
Review
© Georg Thieme Verlag KG Stuttgart · New York

New Insights into the Regulation of Glucagon Secretion by Glucagon-like Peptide-1

J.  Gromada 1 , P.  Rorsman 2
  • 1Department of Pharmacology, University of Aarhus, Universitetsparken, Aarhus C, Denmark
  • 2The Oxford Centre for Diabetes, Endocrinology and Metabolism, The Churchill Hospital, Oxford, UK
Further Information

Publication History

Received 18 August 2004

Accepted after revision 22 August 2004

Publication Date:
18 January 2005 (online)

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Abstract

Glucagon-like peptide-1 (GLP-1) is a potent incretin hormone currently under investigation for use as a novel therapeutic agent in the treatment of type 2 diabetes. One of several therapeutically important biological actions of GLP-1 in type 2 diabetic subjects is ability to induce strong suppression of glucagon secretion. The glucagonostatic action of GLP-1 results from its interaction with a specific G-protein coupled receptor resulting in the activation of adenylate cyclase and an increase in cAMP generation. In the pancreatic α-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion-channel activity and exocytosis of the glucagon-containing granules. In this short review, we will focus on recent advances in our understanding on the cellular mechanisms proposed to underlie the glucagonotropic action of GLP-1 and attempt to incorporate this knowledge into a working model for the control of glucagon secretion. Studies on the effects of GLP-1 on glucagon secretion are relevant to the pathogenesis of type 2 diabetes due to the likely contribution of hyperglucagonemia to impaired glucose tolerance in type 2 diabetes.

Key words

GLP-1 - Incretin - Glucagon - Alpha cell - Islet

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