Effects of allopurinol on insulin action in fructose-fed rats

Objective: To investigate how allopurinol (a xanthine oxidase inhibitor) improves insulin action of rats fed with high-fructose diet. Methods: Male Wistar rats were randomly divided into 3 groups and each group was fed one of the following diets for 4 weeks: standard chow diet, high-fructose diet, and high-fructose diet plus allopurinol. A part of rats in the high-fructose diet plus allopurinol group were infused with a NOS inhibitor, NG-monomethyl-Larginine (L-NMMA), during the euglycemic clamp studies (insulin infusion rate: 3.0mU/kg/min). Insulin sensitivity index was assessed from the oral glucose tolerance test (OGTT). Results: Serum uric acid and plasma insulin concentrations were significantly decreased with allopurinol treatment. High-fructose feeding produced a marked decrease in insulin sensitivity index compared with standard chow diet feeding. Allopurinol treated high-fructose fed rats showed a significant increase in insulin sensitivity index, reaching a similar level as that of the standard chow diet feeding. Infusion of L-NMMA did not change the glucose infusion rate of high-fructose fed rats with allopurinol in the euglycemic clamp. Conclusion: Improvement of insulin action with allopurinol in fructose-fed rats may not be associated with increase in production of nitric oxide.