Effect of Acute and Chronic Losartan Treatment on Glucose Tolerance and Insulin Sensitivity in Fructose-Fed Rats

The purpose of this study was to evaluate the role of angiotensin II (AII) in fructose-treated rats by assessing the effects of acute and chronic losartan treatment on glucose tolerance and insulin sensitivity. The effect of acute losartan treatment was assessed on blood glucose and serum insulin profiles during an intravenous glucose tolerance test (IVGTT) in control and fructose-fed rats. Acute losartan treatment was effective in lowering both blood glucose and plasma insulin profiles in fructose-treated rats during the IVGTT compared to the saline-injected fructose-treated rats. In a subsequent study, 2 weeks after chronic fructose and losartan treatment, IVGTT were performed. Chronic losartan treatment also improved both the glucose tolerance and insuline sensitivit in fructose-treated rats. Additionally chronic losartan treatment also was effective in blocking the hyperinsulinemia, hypertension, and cardiac hypertrophy observed in fructose-fed rats. In neither acute nor chronic studies were there any effects of losartan in control animals. These results strongly suggest that the renin-angiotensin system modulates the insulin resistance, hypertension, and cardiac hypertrophy in fructose-treated rats. Am J Hypertens 1996;9:662–668