New insights into the regulation of glucagon secretion by glucagon-like peptide-1.
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 alpha-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.
Gromada
J
J
Department of Pharmacology, University of Aarhus, Universitetsparken, Aarhus C, Denmark. gromada@lilly.com
Rorsman
P
P
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005934:Glucagon / Q000378:metabolism* / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*; D018027:Receptors, Glucagon / Q000378:metabolism
D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon