Improvement in insulin sensitivity by losartan in non-insulin-dependent diabetic (NIDDM) rats

The present investigation was undertaken to study the effects of chronic tr eatment with losartan (2 mg kg(-1)/day P.O) in neonatal non-insulin-depende nt diabetes mellitus (NTDDM) rats. To induce NIDDM single-dose injection of STZ (70 mg kg(-1); i.p.) was given to 5 day old pups. The animals C, were weaned at 30 days and after a period of 3 months, they were checked for fas ting and fed glucose levels to confirm the status of NIDDM. Losartan (2 mg kg(-1);p.o.) was administered for 6 weeks into the confirmed diabetic rats. A group of control animals were also maintained and this group received sa line 5 days after birth. Fasting and fed glucose levels in NIDDM rats were significantly higher than control rats. Treatment with losartan in the NIDD M rats caused a significant decrease in insulin levels and reduction in ele vated fasting and fed glucose levels. Results of the oral glucose tolerance test (OGTT) showed a significant increase in AUC(glucose) and AUC(insulin) values in NIDDM control rats. Losartan treatment significantly decreased b oth AUCglucose and AUCinsulin values. Insulin sensitivity (K-ITT) index of NIDDM control was significantly low as compared to Wistar control animals f ollowed by significant increase in T-1/2 glucose value. Losartan treatment significantly reversed both KITT and T-1/2 glucose value. Our data indicate s that losartan increases insulin sensitivity in NIDDM rats. (C) 2001 Acade mic Press.