Diabetes-induction reduction in the hepatic accumulation of 70-kDA dextran: role of hyperglycemia and hypoinsulinemia.

In vivo studies were conducted in rats to determine the role of hyperglycemia and hypoinsulinemia in the previously reported reduction in the hepatic accumulation and increase in the serum concentrations of 70-kDa fluorescein-dextran (FD-70) in diabetic (D) rats. The serum, urine, and hepatic concentrations of FD-70 were measured by size exclusion chromatography after i.v. administration of a single doses (5 mg/kg) of FD-70. Intravenous administration of a single 2 IU/kg dose of insulin to D rats at time zero or 4 h after the administration of FD-70 resulted in an increase in some and no change in other animals in their rate of elimination of FD-70 from serum. The presence or absence of a significant insulin effect on the disposition of FD-70 in these animals was, respectively, associated with the presence or absence of a significant insulin-induced hypoglycemic effect. Fasting D rats for 24 h caused normoglycemia, and subsequently, the disposition of FD-70 became similar to that in nondiabetic (ND) rats. Likewise, i.p. injections of glucose to ND rats rendered them hyperglycemic, and the disposition of FD-70 in these rats became similar to that in untreated D animals. However, i.v. injection of glucose, which did not result in sustained hyperglycemia, did not change the disposition of FD-70 in ND rats. Further, the disposition of FD-70 remained unaffected by an i.v. 2 IU/kg dose of insulin administered to ND rats at time zero. Considering all animals, there was a significant negative relationship between the 12-h hepatic recovery of FD-70 and the area under the serum concentration-time curves of glucose. It is concluded that the reduction in the hepatic accumulation of FD-70 in D rats is due to hyperglycemia and not