Sighild Westman

RESPIRATION OF THE β-CELLS IN THE PRESENCE OF SULFONYLUREAS

SUMMARY The hypoglycemic sulfonylureas, tolbutamide, and glibenclamide (HB 419) were found to stimulate the in vitro oxygen consumption of isolated pancreatic islets from obese-hyperglycemic mice. The respiratory rate of the islets increased with the concentration of HB 419 in the range 0.001–0.1 μg/ml, but it did not exceed 120% of the endogenous respiration. In an incubation medium containing glucose at a high concentration (3 mg/ml) the oxygen uptake was slightly inhibited by addition of either tolbutamide or HB 419. Addition of these drugs strongly inhibited the oxygen uptake of islets incubated in the presence of l -leucine. The oxidative decarboxylation of leucine-1-14C was also depressed by the addition of tolbutamide. The oxidation of d -glucose-U-14C remained unaffected when tolbutamide was added to islets incubated in a medium containing 3 mg/ml of glucose. The results are considered representative for the β-cells since this cell type comprises over 90% of the endocrine pancreas of obese hyperglycemic mice. The observations support the view that sulfonylureas stimulate the endogenous substrate oxidation and inhibit the degradation of leucine in the β-cells.