Effect of Imidapril, an Angiotensin-converting Enzyme Inhibitor, on Fructose-induced Insulin Resistance in Rats

Abstract

The effect of imidapril, an angiotensin-converting enzyme (ACE) inhibitor, on insulin resistance was studied in high-fructose-fed rats. A sequential hyperinsulinemic euglycemic clamp procedure (insulin infusion rates: 3 and 30 mU/kg BW/min) was employed in 15 high-fructose-fed rats and 10 normal chow-fed rats under the awake condition. Five of the high-fructose-fed and five of the normal chow-fed rats, respectively, were continuously given imidapril (5 mg/kg BW/min) or saline during the two-step euglycemic clamp study. Furthermore, both imidapril and L-NMMA were infused in another 5 high-fructose-fed rats during the low-dose insulin clamp. Glucose infusion rate (GIR) was regarded as an index of the whole-body insulin action. In the low-dose insulin infusion, the high-fructose feeding resulted in a marked decrease in GIR (p<0.05). Imidapril infusion significantly raised the GIRs in the high-fructose-fed rats (p<0.05). There was no significant difference in GIRs between the chow-fed rats and the imidapril-infused rats with high-fructose diet. In the high-fructose-fed rats, L-NMMA abolished the increase in GIR induced by imidapril (p<0.05). Imidapril did not significantly change the GIRs in the chow-fed rats. In the high-dose insulin infusion, no significant difference in GIR was found among the chow-fed rats, the chow-fed rats given imidapril, the high-fructose-fed rats, and the high-fructose-fed rats given imidapril. These results suggest that, in insulin-resistant rats induced by the high-fructose feeding, an ACE inhibitor, such as imidapril, can improve the whole-body insulin-mediated glucose disposal and that this effect of imidapril is essentially linked to increased activation of NO-pathway.