Abstract
Studies were undertaken to examine cholesterogenesis in the intestine of streptozotocin diabetic rats by measuring incorporation of [2-14C] acetate into cholesterol and 3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase, EC 1. 1. 1. 34) activity. In these diabetic rats, the intestinal mucosal wet weight and the food consumption were markedly increased. Serum insulin levels in these diabetic rats decreased at both noon and midnight. Serum total cholesterol levels were slightly but significantly increased in these diabetic rats. The incorporation of [2-14C] acetate into cholesterol was significantly increased in all diabetic intestinal segments. In addition, the jejunal-ileal gradient in the intestinal cholesterogenesis persisted in the diabetic intestine. On the other hand, it did not affect the rate of fatty acids or carbon dioxide production except in the jejunum. Hepatic HMG-CoA reductase activities were markedly reduced at both noon and midnight in these diabetic rats. The diurnal variation appeared to be nearly abolished. In contrast, the specific activities of this enzyme in the jejunal crypt layer at both noon and midnight were significantly increased in these diabetic rats. In addition, the diurnal variation was observed in the diabetic jejunal crypt layer. Also, total reductase activity per segment in the jejunal and ileal mucosa (villi +crypt layer) was increased in these diabetic rats. The jejunal-ileal gradient in the total reductase activity did not change significantly with streptozotocin diabetes.
The results indicate that in the streptozotocin diabetic rat a marked decrease in cholesterogenesis occurs in the liver, whereas an increase in cholesterogenesis occurs with diurnal variation in the intestine.
