Uncoupling Action of Sulfonylureas on Brown Fat Cells

Tolbutamide markedly enhanced glucose oxidation to carbon dioxide and inhibited lactate formation by rat brown fat cells in the presence of insulin or cysteine. Tolbutamide alone increased oxygen uptake, and this stimulation was enhanced by insulin or cysteine. The effects of tolbutamide were similar to those of carbonyl cyanide m -chlorophenylhydrazone, an uncoupler of oxidative phosphorylation. The increase in glucose oxidation by tolbutamide or the uncoupling agent was not due to time stimulation of glucose metabolism via the pentose shunt pathway. The hypoglycemic sulfonylureas, tolazamide and glyburide, also stimulated glucose oxidation and respiration in the presence of insulin, but to a lesser extent than tolbutamide. Carboxytolbutamide, which has no hypoglycemic action, did not affect brown fat cell metabolism. Tolbutamide also stimulated respiration and glucose oxidation by rabbit brown fat cells in the presence of insulin. Tolbutamide did not affect the oxidation of glucose by white fat cells in either the presence or absence of insulin. Phenformin stimulated lactate formation by rabbit and rat brown fat cells and rat white fat cells. Phenformin inhibited glucose oxidation by rat white or brown fat cells in the presence of insulin. The results suggest that the effects of tolbutamide on brown fat cells are probably due to an uncoupling action, while those of phenformin are due to inhibition of respiration.