title: Regulation of glucagon secretion by incretins.
abstract: Glucagon secretion plays an essential role in the regulation of hepatic glucose production, and elevated fasting and postprandial plasma glucagon concentrations in patients with type 2 diabetes (T2DM) contribute to their hyperglycaemia. The reason for the hyperglucagonaemia is unclear, but recent studies have shown lack of suppression after oral but preserved suppression after isoglycaemic intravenous glucose, pointing to factors from the gut. Gastrointestinal hormones that are secreted in response to oral glucose include glucagon-like peptide-1 (GLP-1) that strongly inhibits glucagon secretion, and GLP-2 and GIP, both of which stimulate secretion. When the three hormones are given together on top of isoglycaemic intravenous glucose, glucagon suppression is delayed in a manner similar to that observed after oral glucose. Studies with the GLP-1 receptor antagonist, exendin 9-39, suggest that endogenous GLP-1 plays an important role in regulation of glucagon secretion during fasting as well as postprandially. The mechanisms whereby GLP-1 regulates glucagon secretion are debated, but studies in isolated perfused rat pancreas point to an important role for a paracrine regulation by somatostatin from neighbouring D cells. Clinical studies of the antidiabetic effect of GLP-1 in T2DM suggest that the inhibition of glucagon secretion is as important as the stimulation of insulin secretion.
authors.affiliation: Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark. jjholst@sund.ku.dk
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: M
authors.initials: M
authors.lastname: Christensen
authors.forename: A
authors.initials: A
authors.lastname: Lund
authors.forename: J
authors.initials: J
authors.lastname: de Heer
authors.forename: B
authors.initials: B
authors.lastname: Svendsen
authors.forename: U
authors.initials: U
authors.lastname: Kielgast
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*
chemical_list: C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon