Impact of Exogenous Hyperglucagonemia on Postprandial Concentrations of Gastric Inhibitory Polypeptide and Glucagon-Like Peptide-1 in Humans

Abstract

Postprandial secretion of glucagon-like peptide 1 (GLP-1) has been found diminished in some patients with type 2 diabetes mellitus (T2DM) and high glucagon concentrations. We examined the effects of exogenous glucagon on the release of incretin hormones. Ten patients with T2DM and 10 healthy controls were examined with a meal test during the iv administration of glucagon 0.65 ng/kg.min and placebo. GLP-1 plasma concentration increased after meal ingestion in both groups (P<0.0001), but postprandial GLP-1 plasma levels were not affected by glucagon administration. However, immediately after cessation of the glucagon infusion, GLP-1 levels increased by about 2-fold to levels of 51.8+/-14.6 pmol/liter in the T2DM patients and 58.9+/-20.0 pmol/liter in controls (P<0.05). The time courses of glucose-dependent insulinotropic peptide glucose-dependent insulinotropic peptide and GLP-1 concentrations were not different between T2DM patients and controls during the placebo experiments (P=0.33 and P=0.13, respectively). Glucose concentrations were increased by glucagon administration in controls (P<0.05, respectively), but insulin and C-peptide levels were not affected. Gastric emptying was slightly delayed by glucagon administration in controls (P<0.05) but not in T2DM patients (P=0.77). Exogenous glucagon does not directly inhibit incretin secretion. However, a decline in circulating glucagon levels may exert a permissive effect on GLP-1 release. This might contribute to the reduction in GLP-1 concentrations found in some patients with T2DM.