Biliary excretion of organic anions in diabetic rats

Little definitive data are available concerning the effects of insulin deficiency on the hepatic uptake and biliary excretion of endogenous or xenobiotic substances. To expand our understanding of this area, male Sprague-Dawley rats were pretreated with streptozotocin (45 mg/kg i.v.) to induce uncontrolled diabetes. Four to five weeks later, diabetic rats exhibited elevations in serum glucose (640 +/- 13 mg/dl), biliary glucose (307 +/- 35 mg/dl), urine output (166 +/- 11 ml/24 hr), basal bile flow rate (73 +/- 2 microliter/min/kg), liver weight/body weight ratio and bile acid pool size. Polyphagia and generalized muscle atrophy were also evident. Plasma disappearance and biliary excretion of several organic anions were studied after i.v. administration. There were no differences between control and diabetic rats in the plasma elimination and biliary excretion of eosin, phenol-3,6-dibromphthalein disulfonate and sulfobromophthalein. Although hepatic uptake was unchanged, the biliary excretion of amaranth was decreased 30% in diabetic rats. There were no differences in bile flow rate in control or diabetic rats after administration of these four anions. In contrast, administration of indocyanine green, bromcresol green and rose bengal did not depress bile flow in diabetic rats as was observed in control rats. In addition, the rate of maximal biliary excretion was increased by 390, 240 and 151% for rose bengal, indocyanine green and bromcresol green, respectively. Plasma clearance of rose bengal was 65% higher in diabetic rats. Total body clearance and steady-state volume of distribution values for all other anions were not different after induction of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)