Spontaneously diabetic biobreeding rats and impairment of bile acid-independent bile flow and increased biliary bilirubin, calcium and lipid secretion.

Chemically induced diabetes has been reported to induce profound changes in bile formation, but possible toxic effects of the streptozotocin or alloxan used cannot be excluded totally. This study was undertaken to evaluate biliary function in spontaneously diabetic female biobreeding rats with a diabetes duration of 2 wk and compare them with nondiabetic littermates. Diabetic animals evidenced glycosuria, hyperglycemia and hypoinsulinemia. Biliary concentration and secretion of bile acids, cholesterol and phospholipids were significantly increased, with no enhancement in the lithogenic index of bile. Bile flow and the biliary secretion of sodium, potassium, chloride and bicarbonate were significantly reduced despite the increased bile acid secretion. The cholestatic condition was confirmed by an increased serum concentration of bile acids and a higher activity in serum of the alkaline phosphatase liver isoenzyme. Biliary calcium concentration increased without any change in its serum concentration. A linear relationship was observed between biliary calcium and bile acid secretion. Serum concentration of unconjugated and of conjugated bilirubin was increased 1.6-fold and 8-fold, respectively, with a 1.5-fold enhanced biliary secretion of bilirubins despite the cholestasis; this points to an enhanced bilirubin production. An increased proportion of conjugated bilirubin was found in serum together with an enhanced bilirubin diconjugate/monoconjugate ratio in bile. A higher UDP-glucuronyltransferase activity and a delayed transit of bilirubin could account for these effects. Administration of insulin to diabetic animals tended to reverse the above reported changes. The spontaneously diabetic biobreeding rat thus represents a model of bile acid-independent cholestasis with enhanced biliary bile acid and calcium secretion and with presumably an enhanced bilirubin production.