Effect of sodium orthovanadate on the hepatobiliary clearance of rose bengal in streptozotocin-induced diabetic rats

Abstract

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 alter 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 Sprague-Dawley rats were used: normal, insulin-treated normal, vanadate-treated 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 orthovanadate (877 ± 82 μmol/kg/day, p.o.) treatments were initiated. After 4 weeks, the clearance and biliary excretion of rose bengal (60 μmol/kg, i.v.) were determined for 3 hr. Bile flow rate, rose bengal excretion, and excretion of endogenous bile acids were unchanged in the two treated normal groups inthe insulin-treated diabetic rats. These parameters were increased in untreated diabetic and vanadate-treated diabetic rats as compared with normal. Pharmacokinetic analyses indicated that total and biliary clearances of rose bengal were increased in diabetic rats and orthovanadate did not reverse these changes. However, liver weight and serum glucose concentrations were reduced by orthovanadate treatment. These data indicate that the oral insulinomimeric chemical sodium orthovanadate effectively reversed some, but not all, of the diabetes-induced alterations of hepatic function.