Failure of Diazoxide to Affect Carbohydrate Metabolism of the Isolated Liver

It has been reported that diazoxide stimulates hepatic glycogenolysis and inhibits hepatic glucose uptake. In order to determine whether these effects reflect direct action of the drug on the liver, the effect of diazoxide on the isolated perfused rat liver was investigated. Exposure of glycogen-containing livers to concentrations of diazoxide as high as 180 μg./ml. for as long as four hours did not result in decrease in liver glycogen, increase in hepatic glucose output, or increase in urea production. Diazoxide did not inhibit glucose uptake and glycogen deposition by glycogendepleted livers presented with glucose loads. It is concluded that direct action on the liver is not a contributory mechanism to the diabetogenic effect of diazoxide.