Effects of troglitazone on hyperglycemia-induced insulin resistance

Background. Troglitazone is a new class of oral hypoglycemic agent and improves insulin action both in NIDDM and nondiabetic insulin resistance such as fructose-fed rats. We performed this study to examine the effects of troglitazone on the nongenetic hyperglycemia-induced insulin resistance. Methods. Male Sprague-Dawley rats were divided into three groups and were fed normal rat chow and chow admired with troglitazone (0.2%) for 2 weeks. Rats were infused with normal saline or 30% dextrose for 6.5 h with somatostatin (8 mu g/kg/min) followed by euglycemic hyperinsulinemic clamp study. Results. 1) There was no significant difference in body weight among the three groups of rats. 2) Basal plasma glucose levels were significantly elevated in the hyperglycemia group and the troglitazone-treated group (p<0.05). 3) There was no significant difference in basal insulin level among the three groups of rats. 4) Maximal GDR was significantly decreased in the hyperglycemia group compared to the control-and troglitazone-treated group, respectively. 5) Steady-state plasma free fatty acid concentration was significantly elevated in the hyperglycemia and troglitazone groups, however, there was no significant difference between the hyperglycemia group and the troglitazone-treated group. Conclusion. These results suggest that a 6.5-h glucose infusion leads to significant insulin resistance and prior troglitazone treatment restores insulin action to near normal.