Assessment of diabetogenic drug activity in the rat: 5,5-diphenyl-2-thiohydantoin

Abstract

The diabetogenic activity of 5,5-diphenyl-2-thiohydantoin (DPTH) via oral administration was assessed in both normal and streptozotocin diabetic rats. Rats were fed powdered chow diet with and without 0.1% (w/w) DPTH. Food consumption and body weight were recorded every other day; whole blood glucose concentrations were determined at the start of the study and at the midpoint. At sacrifice, liver and pancreas were excised and blood samples were collected. Protein and lipid levels were determined in liver; insulin in pancreas; and glucose, insulin, and lipid in blood. DPTH treatment caused decreased food consumption and body weight gain. The drug dose, calculated from the food consumption data, was 76.5 mg/kg/day for the normal rats and 107 mg/kg/day for the diabetic rats. DPTH increased liver weight and liver lipid content in both normal and diabetic rats, and markedly lowered serum triglyceride concentration in normal rats but not in diabetic rats. Serum fatty acid concentration was not altered by DPTH. DPTH produced a significant elevation of blood glucose concentration of the diabetic rats that was not, however, correlated with altered pancreatic insulin concentration. In vitro, DPTH infusion inhibited insulin secretion by the perfused pancreas.