Uncoupling effect of hypoglycemic sulphonylureas on the isolated rat liver mitochondria.

The effect of several hypoglycemic sulphonylureas upon the oxidative phosphorylation of intact rat liver mitochondria was examined. Following results were obtained and discussed in relation to hypoglycemic action and uncoupling site of these drugs. 1. All hypoglycemic sulphonylurea drugs tested, i.e., tolbutamide, carbutamide, chlorpropamide, acetohexamide, glybenclamide, and glyclopyramide were found to be uncouplers to the intact rat liver mitochonbria. 2. They were also found to decrease respiratory release of 20 ,uM DNP. 3. Sulphonylureas could induce latent ATPase activity of intact rat liver mitochondria. ATPase activity induced by glybenclamide was reduced to zero by the addition of rutamycin just like DNP. 4, Judging from the above data, uncoupling site of sulphonylureas may be near DNP site.