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

The present investigation was undertaken to study the effects of chronic treatment with losartan (2 mg kg(-1)/ day P.O) in neonatal non-insulin-dependent diabetes mellitus (NIDDM) rats. To induce NIDDM single-dose injection of STZ (70 mg kg(-1); i.p.) was given to 5 day old pups. The animals were weaned at 30 days and after a period of 3 months, they were checked for fasting 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 saline 5 days after birth. Fasting and fed glucose levels in NIDDM rats were significantly higher than control rats. Treatment with losartan in the NIDDM rats caused a significant decrease in insulin levels and reduction in elevated 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 both AUC(glucose)and AUC(insulin)values. Insulin sensitivity (K(ITT)) index of NIDDM control was significantly low as compared to Wistar control animals followed by significant increase in T(1/2)glucose value. Losartan treatment significantly reversed both K(ITT)and T(1/2)glucose value. Our data indicates that losartan increases insulin sensitivity in NIDDM rats.