D-Fenfluramine (D-Fen) Improves Insulin Sensitivity and Glucose Tolerance in Insulin-Deficient Rats

Abstract

D-Fen, a widely used anorectic drug, is reported to improve insulin sensitivity and glycaemic control in human non-insulin dependent diabetes independently of its anorectic effect. A dose renge of 0.5, 1.0, 2.5, 5.0 mg/kg of D-fen was given by gavage to male Wistar rats (n=10) that had been made diabetic by streptozotocin (55 mg/kg) for 3 weeks. The untreated diabetic group and nondiabetic group received water by gavage. After 24 h food deprivation, glucose (1 g/kg) was given by gavage to all 3 groups, 2 hours after D-fen or water treatment and 15-minute tail-prick blood samples (5ul) were collected for 2 h to assess the effects of D-fen on glucose tolerance. D-fen significantly reduced glucose levels only at the 5 mg/kg dose during the 2 hours before and during the glucose tolerance test compared with the untreated diabetic and non-diabetic groups, peak delta glucose (D-fen 0.23±0.2 mnol/l vs untreated diabetic 5.2±1.2,p<0.001; D-fen 0.23±0.2 vs non-diabetic 3.5±0.4, p<O.OOl). Final insulin levels in D-fen treated diabetic rats were not significantly different from untreated diabetics, whereas both diabetic groups were significantly different from non-diabetic rats (D-fen 19.922.5 pmol/l vs non-diabetic 362±46, p<O.OOl; non-diabetic 362±46 vs untreated diab. 24.1±4, p<O.OOl). It would appear that D-fen has a profound effect on insulin sensitivity in streptozotocin-diabetic rats.