The effects of glucose-dependent insulinotropic polypeptide infused at physiological concentrations in normal subjects and Type 2 (non-insulin-dependent) diabetic patients on glucose tolerance and B-cell secretion

Summary The effects of porcine glucose-dependent insulinotropic polypeptide given by continuous intravenous infusion in normal subjects (n=6) and Type 2 (non-insulin-dependent) diabetic patients (n=6) have been investigated. The subjects were studied on 2 separate days after overnight fasts. On each day 25 g of glucose was infused from 0–30 min plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (0.75 pmol·kg^–1·min^–1) or control solution. During the glucose-dependent insulinotropic polypeptide infusion plasma glucose values were reduced in normal subjects from 30–60 min (p<0.01) and in Type 2 diabetic patients at 45 and 60 min (p<0.05). In the normal subjects insulin concentrations were greater from 10–35 min (p<0.01) following glucose-dependent insulinotropic polypeptide infusion and peak values were increased by 123%. In the Type 2 diabetic patients following glucose-dependent insulinotropic polypeptide infusion insulin levels were increased from 4–40 min (p<0.01) but peak values were only increased by 27%. In the normal subjects C-peptide values were greater from 25–45 min (p<0.01) following glucose-dependent insulinotropic polypeptide infusion and peak C-peptide levels were increased by 82%. In the Type 2 diabetic patients following the glucose-dependent insulinotropic polypeptide infusion C-peptide levels were increased from 6–55 min (p<0.01) and peak values were increased by 20%. Plasma glucose-dependent insulinotropic polypeptide levels were within the physiological post prandial range during the glucose-dependent insulinotropic polypeptide infusion. Glucose-dependent insulinotropic polypeptide is insulinotropic in normal subjects and Type 2 diabetic patients at physiological concentrations and results in improved glucose tolerance. This insulinotropic effect is less marked in the diabetic patients and may represent insensitivity of the B cell to glucose-dependent insulinotropic polypeptide.