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
