Intestinal and Hepatic Cholesterol Synthesis in the Alloxan Diabetic Rat 1

Abstract

The effects of alloxan diabetes and insulin treatment upon rat 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was studied. In diabetes, hepatic HMG-CoA reductase specific and whole organ activities were reduced 85 and 89%, respectively, during the diurnal high period of enzyme activity. In contrast, whole small intestinal HMG-CoA reductase activity was increased twofold in diabetic rats during this period. The diabetic rats' whole gut HMG-CoA reductase activity approximated the entire liver's. Chronic insulin therapy markedly stimulated hepatic HMG-CoA reductase activity in diabetes rats but did not increase gut enzyme activity. Thus in alloxan diabetes, the intestine may be as important a source of endogenous cholesterol as the liver.