Does glibenclamide influence the clearance of insulin and glucose uptake in patients with type 2 diabetes mellitus?

Sulphonylureas have been proposed to decrease the clearance of insulin based on the finding that they increase peripheral insulin concentrations more than C-peptide concentrations. However, direct evidence for such an effect has so far been lacking. The aim of this study was to investigate whether glibenclamide affects clearance of insulin in Type 2 diabetic patients. Nine patients with Type-2 diabetes participated in the study. Insulin clearance and glucose metabolism was assessed with a 240 min euglycaemic insulin clamp in combination with infusion of somatostatin (400 micrograms h-1) to completely suppress endogenous insulin secretion. Either saline or glibenclamide was infused throughout the clamp in random order. During both the glibenclamide and the saline protocol the C-peptide level declined to < 0.07 nmol l-1 within 150 min, indicating that insulin secretion was completely suppressed. However, peripheral clamp insulin concentrations remained similar during both saline and glibenclamide protocols (3374 +/- 258 vs. 3350 +/- 265 pmol l-1 x 240 min, p = NS). There was no significant difference in the metabolic clearance rate of insulin during the glibenclamide compared to the saline experiment neither during the first 120 min (796 +/- 36 vs. 757 +/- 34 ml m-2min-1) nor during the last 2 h of the clamp (780 +/- 43 vs. 724 +/- 35 ml m-2min-1). Total glucose metabolism during the first two (14 +/- 2 vs. 15 +/- 2 mumol kg-1 min-1) and the last 2 h of the clamp was similar both during saline and glibenclamide infusions (27 +/- 4 vs. 28 +/- 4 mumol kg-1min-1).(ABSTRACT TRUNCATED AT 250 WORDS)