EFFECT OF BENFLUOREX ON INSULIN-SECRETION AND INSULIN ACTION IN STREPTOZOTOCIN-DIABETIC RATS

We have examined the effect of chronic (20 days) oral administration o f benfluorex (35 mg/kg) in a rat model of non-insulin-dependent diabet es mellitus (NIDDM), as induced by injection of streptozotocin 5 days after birth and characterized by frank hyperglycaemia, hypoinsulinaemi a, and hepatic and peripheral insulin resistance. In the benfluorex-tr eated diabetic rats, basal plasma glucose levels were decreased (7.9 /- 0.2 mM as compared with 17.2 +/- 1.1 mM in the pair-fed untreated d iabetic and 6.7 +/- 0.2 mM in the benfluorex-treated non-diabetic rats ) while the basal and the glucose-stimulated (IVGTT) plasma insulin le vels were not improved. The lack of improvement of glucose-induced ins ulin release after benfluorex treatment was confirmed under in vitro c onditions (perfused pancreas). In the benfluorex-treated diabetic rats , basal glucose production and overall glucose utilization were normal ized. Following hyperinsulinaemia (euglycaemic clamp), glucose product ion was normally suppressed while overall glucose utilization was not significantly improved. Since benfluorex exerts a predominant action o n the liver in the present rat model of diabetes, and since increased basal hepatic glucose output is a major metabolic abnormality and is r esponsible for much of the elevated fasting blood glucose levels in NI DDM, the use of such a compound in NIDDM may be potentially relevant.