The effect of pioglitazone on glucose metabolism and insulin uptake in the perfused liver and hindquarter of high-fructose—fed rats

Abstract

To investigate the effect of pioglitazone, a thiazolidinedione oral antidiabetic agent, on the glucose and insulin metabolism in insulin resistance, a perfusion study of the liver and hindquarter was performed in high-fructose—fed rats. Male Wistar albino rats were assigned randomly to one of the following diets for 2 weeks: (1) normal chow (control group), (2) a diet high in fructose (fructose group), or (3) a high-fructose diet plus pioglitazone (pioglitazone intake of ≅ 10 mg/kg body weight; pioglitazone group). The elevated levels of plasma insulin, triglyceride, and free fatty acids (FFA) in the fructose group were normalized by pioglitazone administration. In the perfused liver, the glucagon-induced increment in the glucose output of the fructose (57.1 ± 9.1 μmol/g liver/20 min) and pioglitazone (44.7 ± 10.1 μmol/g liver/20 min) groups was significantly ( P < .01) higher than that in the control group (27.6 ± 5.7 μmol/g liver/20 min). The level in the pioglitazone group was significantly ( P < .05) lower than that in the fructose group. In the presence of 100 or 500 μU/mL insulin, the insulin-mediated decrement in the glucagon-induced glucose output of the fructose group (29.8 ± 7.8 or 38.9 ± 9.3 μmol/g liver/20 min) was significantly ( P < .05) lower than that in the control (45.8 ± 14.2 or 54.5 ± 8.5 μmol/g liver/20 min) and pioglitazone (44.4 ± 9.2 or 56.2 ± 10.8 μmol/g liver/20 min) groups, respectively. In the perfused hindquarter, glucose uptake in the fructose group (8.2 ± 2.0 μmol/g muscle/30 min) was significantly ( P < .05) lower than that in the control (12.1 ± 2.3 μmol/g muscle/30 min) and pioglitazone (11.8 ± 3.1 μmol/g muscle/30 min) groups. In the presence of 100 or 50 μU/mL insulin, glucose uptake in the fructose group (12.0 ± 5.2 or 17.4 ± 3.0 μmol/g muscle/30 min) was significantly ( P < .05) lower than that in the control (20.2 ± 2.4 or 23.0 ± 3.1 μmol/g muscle/30 min) and pioglitazone (17.8 ± 2.4 or 20.7 ± 2.0 μmol/g muscle/30 min) groups, respectively. Insulin uptake by the liver and hindquarter was not significantly different in the control, fructose, and pioglitazone groups. These results indicate that pioglitazone improves the increased glucagon-induced hepatic glucose output and decreases insulin-induced muscular glucose uptake without altering insulin uptake in high-froctose—fed insulin-resistant rats.