ALTERED BILE-ACID METABOLISM IN ALLOXAN DIABETIC RATS

Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum, liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained unchanged. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxycholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and α-, β- and ω-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged. Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7α-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40 %. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats. © 1979, The Japanese Pharmacological Society. All rights reserved.