HEPATOBILIARY EXCRETION OF BILE-ACIDS AND ROSE-BENGAL IN STREPTOZOTOCIN-INDUCED AND GENETIC DIABETIC RATS

Divergent opinions regarding the effect of streptozotocin-(STZ) induce d diabetes on bile flow rate may be due to the differing lengths of ti me after STZ administration at which bile flow was measured. Also, the biliary excretion of bile acids can influence the canalicular transpo rt of several organic anions. Therefore, the hepatic clearance of the bile acid-dependent organic anion rose bengal was studied over a 30-da y period in STZ-induced insulin-dependent Sprague-Dawley diabetic rats with elevated bile acid pools and in fatty noninsulin-dependent diabe tic and lean Wistar rats. Excretion of total bile acids and rose benga l was higher in diabetic rats than in Sprague-Dawley control or lean o r fatty Wistar rats. Depletion of bile acids for 10 hr in the 30-day S TZ rat prevented the increased excretion of rose bengal. Bile flow rat es in fatty and lean Wistar rats were similar to that in Sprague-Dawle y controls. Increased bile acid excretion 7 and 14 days after STZ was not accompanied by the expected significant increase in bile flow, ref lecting decreased bile acid-independent bile flow, regardless of metho d of calculation of bile flow (per g liver or per kg body weight). By 30 days, there were significant increases in bile acid excretion and b ile flow. The increased clearance of rose bengal 7 days after STZ indi cates that pathophysiological changes in the hepatocyte begin soon aft er the initiation of diabetes. Studies of taurocholate uptake into liv er plasma membrane vesicles indicated that the maximal velocity of tra nsport across the basolateral membrane was increased with no change in K-m. This change was not observed in vesicles from insulin-treated di abetic rats. Therefore, studies employing STZ need to allow time for S TZ toxicity to be overcome and for the pathology of diabetes to become established, to accurately reflect the diabetic condition.