Changes in hepatic and intestinal cholesterol regulatory enzymes. The influence of metformin
Abstract
The effect of metformin (N,N-dimethylbiguanide) on the rate-limiting enzymes of cholesterol metabolism was observed. 3-Hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and acyl-CoA-cholesterol acyltransferase (ACAT) activities were estimated in hepatic microsomal and intestinal cell preparations from normal and alloxan-diabetic rats. Metformin administration had no effect on either hepatic enzyme. Intestinal ACAT activity was significantly decreased in the metformin-treated rats when compared with controls (P less than 0.001). Intestinal HMG-CoA reductase activity was not significantly affected. Diabetic rats showed a significantly higher intestinal HMG-CoA reductase activity when compared with controls (P less than 0.001). Intestinal ACAT activity in the diabetic group was similar to control values. Metformin administration to diabetic rats caused a marked decrease in both intestinal HMG-CoA reductase activity (P less than 0.001) and ACAT activity (P less than 0.002). It is concluded that the effect of metformin on the intestinal cholesterol enzyme system may be responsible for its cholesterol-lowering action.
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