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

Background: 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. Patients and Methods: 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. Results: 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). Conclusions: 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. A decline in circulating glucagon levels may exert a permissive effect on GLP-1 release that may contribute to the reduction in GLP-1 concentrations found in some patients with type 2 diabetes.