EFFECT OF SODIUM ORTHOVANADATE ON THE HEPATOBILIARY CLEARANCE OF ROSE-BENGAL IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Sodium orthovanadate is known to promote glucose uptake in muscle and adipose tissues and has been suggested as a possible oral hypoglycemic agent. In addition, insulin-dependent diabetes has been shown to alte r the hepatobiliary clearance of several drugs in rats. This study has determined whether orthovanadate, like insulin, can reverse diabetes- induced changes in the biliary excretion of endogenous bile acids and in the hepatobiliary clearance of rose bengal. Six groups of male Spra gue-Dawley rats were used: normal, insulin-treated normal, vanadate-tr eated normal, diabetic, insulin-treated diabetic, and vanadate-treated diabetic. Diabetes was induced by injection of streptozotocin (45 mg/ kg, i.v.). One week later, insulin (2-4 U/day, s.c.) and sodium orthov anadate (877 +/- 82 mu mol/kg/day, p.o.) treatments were initiated. Af ter 4 weeks, the clearance and biliary excretion of rose bengal (60 mu mol/kg, i.v.) were determined for 3 hr. Bile flow rate, rose bengal e xcretion, and excretion of endogenous bile acids were unchanged in the two treated normal groups and in the insulin-treated diabetic rats. T hese parameters were increased in untreated diabetic and vanadate-trea ted diabetic rats as compared with normal. Pharmacokinetic analyses in dicated that total and biliary clearances of rose bengal were increase d in diabetic rats and that orthovanadate did not reverse these change s. However, liver weight and serum glucose concentrations were reduced by orthovanadate treatment. These data indicate that the oral insulin omimetic chemical sodium orthovanadate effectively reversed some, but not all, of the diabetes-induced alterations of hepatic function.