Effect of sulphonylurea on glucose-stimulated insulin secretion in healthy and non-insulin dependent diabetic subjects: a dose-response study

• Published in: Acta diabetologica Vol. 28; no. 2; p. 162
• Main Authors: Groop, L C, Ratheiser, K, Luzi, L, Melander, A, Simonson, D C, Petrides, A, Bonadonna, R C, Widén, E, DeFronzo, R A
• Format: Journal Article
• Language: English
• Published: Germany 1991
• Subjects: Adult; Analysis of Variance; Blood Glucose - metabolism; C-Peptide - blood; C-Peptide - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Female; Glipizide - pharmacology; Glucose - pharmacology; Glucose Clamp Technique; Humans; Insulin - blood; Insulin - metabolism; Insulin Secretion; Kinetics; Male; Middle Aged; Reference Values; Time Factors
• ISSN: 0940-5429
• DOI: 10.1007/bf00579720

The effect of a rapid-acting sulphonylurea, glipizide, on the dose-response relationship between the beta-cell response (insulin and C-peptide secretion) and the ambient plasma glucose concentration was examined in 12 healthy and 6 non-insulin-dependent diabetic subjects. The subjects participated in two sets of experiments which were performed in random order: (A) four hyperglycaemic clamp studies, during which the plasma glucose concentration was raised for 120 min by 1 (only in healthy subjects), 3, 7, and 17 mmol/l; and (B) the same four hyperglycaemic clamp studies preceded by ingestion of 5 mg glipizide. All subjects participated in a further study, in which glipizide was ingested and the plasma glucose concentration was maintained at the basal level. In control subjects in the absence of glipizide, the first-phase plasma insulin response (0-10 min) increased progressively with increasing plasma glucose concentration up to 10 mmol/l, above which it tended to plateau. Glipizide augmented the first-phase insulin response without changing the slope of the regression line relating plasma insulin to glucose concentrations. The second-phase plasma insulin response (20-120 min) increased linearly with increasing hyperglycaemia (r = 0.997). Glipizide alone increased the plasma insulin response by 180 pmol/l. A similar increase in plasma insulin response following glipizide was observed at each hyperglycaemic step, indicating that glipizide did not affect the sensitivity of the beta-cell to glucose. First-phase insulin secretion was reduced in the type 2 (non-insulin-dependent) diabetic patients, and was not influenced by glipizide.