Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man

Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first-and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic glucose clamp. Twelve healthy male subjects, age (mean+/-SEM) 22.5+/-0.5 years, body mass index (BMI) 21.7+/- 0.6 kg m(-2), were studied in a randomized, double-blind study design. Glibenclamide 10 mg or placebo was taken before a 4-h hyperglycaemic clamp (blood glucose 8 mmol L-1 during the first 2h and 32 mmol L-1 during the next 2h). During hyperglycaemic clamp at 8 mmol L-1, the areas under the Delta insulin curve (AUC(Delta insulin), mean +/- SEM) from 0 to 10 min (first phase) were not different: 1007 +/- 235 vs. 1059 +/- 261 pmol L-1 x 10 min (with and without glibenclamide, P=0.81). However, glibenclamide led to a significantly larger increase in AUC(Delta insulin) from 30 to 120 min (second phase): 16 087 +/- 4489 vs. 7107 +/- 1533 pmol L-1 x 90 min (with and without glibenclamide respectively, P <0.03). The same was true for AUC(Delta C-peptide): no difference from 0 to 10 min but a significantly higher AUC(Delta C-peptide) from 30 to 120 min on the glibenclamide day (P <0.01).; The M/I ratio (mean glucose infusion rate divided by mean plasma insulin concentration) from 60 to 120 min, a measure of insulin sensitivity, did not change: 0.26 +/- 0.05 vs. 0.22 +/- 0.03 mu mol kg(-1) min(-1) pmol L-1 (with and without glibenclamide, P=0.64). During hypergly -caemic clamp at 32 mmol L-1, the AUC(Delta insulin) from 120 to 130 min (first phase) was not different on both study days: 2411 +/- 640 vs. 3193 +/- 866 pmol L-1 x 10 min (with and without glibencIamide, P=0.29). AUC(Delta insulin), from 150 to 240 min (second phase) also showed no difference: 59623 +/- 8735 vs. 77389 +/- 15161 pmol L-1 x 90 min (with and without glibenclamide, P=0.24). AUC(Delta C-peptide) from 120 to 130 min and from 150 to 240 min were slightly lower on the glibenclamide study day (both