BILE-ACID POOL CHANGES AND REGULATION OF CHOLATE SYNTHESIS IN EXPERIMENTAL DIABETES
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1978
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Abstract
The effect of alloxan-diabetes and insulin treatment in bile acid pool size and composition, bile acid secretion and cholic acid synthesis was investigated in the rat. The size of the cholate pool was significantly increased 4 days after diabetes induction. It reached a constant size 3 times that of control animals after 2 wk of diabetes. Changes in bile acid pool size and secretion were directly dependent on the insulin deficiency state since they were reversed by insulin treatment and were not influenced by the caloric intake of the animal nor the pharmacologic effect of alloxan. Biliary cholate secretion was also 3-fold increased in diabetic rats and it accounted for more than 80% of the total bile acids compared to 60% in the control group. The calculated daily rate of cholate synthesis was increased in diabetic rats and the circadian rhythm of cholate synthesis was abolished in this condition. The negative feedback mechanism that regulates bile acid synthesis was deleted in diabetes and was partially restored after 2 wk of insulin treatment. Bile acid metabolism was profoundly changed in alloxan-diabetic rats. Insulin may play an important role in the regulation of bile acid synthesis and intestinal absorption.