Anaplerotic amino acids attenuate glucagon secretion by lowering cAMP

Abstract

The second messenger cAMP potentiates pancreatic α-cell glucagon secretion, which is critical for maintaining blood glucose homeostasis. Glucose regulates cAMP both intrinsically and extrinsically, by stimulating δ-cell somatostatin, however the ability of amino acids to control αcell cAMP has not been examined despite their glucagonotropic effect. Using mouse islet perifusion assays to simultaneously assess insulin and glucagon release, mixed amino acids (QLRA; glutamine, leucine, arginine, and alanine) elicited a large, biphasic glucagon response that was dampened by glucose elevation.