Suppression by exendin(9-39)amide of glucagon-like peptide-1 insulinotropic action in rats infused with dimethyl ester of succinic acid.

Abstract

Glucagon-like peptide-1 (GLP-1) acts as a nutrient-dependent insulin-releasing agent, and its insulinotropic action is enhanced by nutrient secretagogues, such as the dimethyl ester of succinic acid (SAD). In the present study, a primed constant infusion of SAD (0.5 micromol followed by 0.25 micromol/min both per g of body wt) was found to increase plasma insulin concentration in fed anesthetized rats, to potentiate the B-cell secretory response to GLP-1 (0.5 pmol/g of body wt), and to unmask the hypoglycemic potential of the gastrointestinal hormone. In the SAD-infused rats, the infusion of exendin(9-39)amide (5.0 pmol/min per g of body wt), 1 min before and 3 min after GLP-1 injection, decreased plasma insulin concentration before GLP-1 injection, suppressed the B-cell secretory response to GLP-1, and both delayed and minimized its hypoglycemic action. It is proposed, therefore, that exendin (9-39)amide could represent a tool in the treatment of alimentary or reactive hypoglycemia.