Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and healthy control subjects

Abstract

A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a characteristic of patients with type 2 diabetes. It was the aim of this study to determine the response of insulin secretion to different GIP doses administered by intravenous bolus injection and via continuous infusion in both healthy subjects and patients with type 2 diabetes. Eight patients with type 2 diabetes and eight healthy subjects participated in a 240-min hyperglycemic clamp (140 mg/dl) with intravenous infusion of placebo, GIP at a low dose, and GIP at a high dose, each administered continuously over 60 min. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at 0, 60, and 120 min, respectively. Capillary and venous blood was drawn for glucose, insulin, C-peptide, and GIP. Plasma insulin and C-peptide concentrations were lower in patients than in control subjects during all infusion periods. GIP bolus administration evoked a significant increase in plasma insulin levels in both patients with type 2 diabetes and healthy subjects. In contrast, the continuous GIP infusion led to a weak increase in insulin secretion in both healthy subjects and type 2 diabetic patients. The dose-response relationship for the increase in insulin secretion after GIP bolus administration was similar in both groups, although at different degrees of beta-cell function. The stimulation of insulin secretion by GIP is stronger after its bolus administration than during continuous infusion. Even though the insulin secretory capacity is generally impaired in patients with type 2 diabetes, the relative sensitivity of insulin secretion to a bolus administration of GIP is almost preserved. Therefore, the existence of a specific GIP receptor defect in type 2 diabetes appears unlikely.