Intestinal and Hepatic Cholesterol Synthesis in the Alloxan Diabetic Rat

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Abstract
The effects of alloxan diabetes and insulin treatment upon rat 3-hydroxy-3-methylglutaryl CoA (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 2-fold 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 diabetic, the intestine may be as important a source of endogenous cholesterol as the liver.