Ikeda T, Fujiyama K
Tottori University College of Medical Care Technology, and Chukai Hospital, Yonago, Japan.
Metabolism. 1998 Sep;47(9):1152-5. doi: 10.1016/s0026-0495(98)90292-x.
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 approximately 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 micromol/g liver/20 min) and pioglitazone (44.7+/-10.1 micromol/g liver/20 min) groups was significantly (P < .01) higher than that in the control group (27.6+/-5.7 micromol/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 microU/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 micromol/g liver/20 min) was significantly (P < .05) lower than that in the control (45.8+/-14.2 or 54.5+/-8.5 micromol/g liver/20 min) and pioglitazone (44.4+/-9.2 or 56.2+/-10.8 micromol/g liver/20 min) groups, respectively. In the perfused hindquarter, glucose uptake in the fructose group (8.2+/-2.0 micromol/g muscle/30 min) was significantly (P < .05) lower than that in the control (12.1+/-2.3 micromol/g muscle/30 min) and pioglitazone (11.8+/-3.1 micromol/g muscle/30 min) groups. In the presence of 100 or 500 microU/mL insulin, glucose uptake in the fructose group (12.0+/-5.2 or 17.4+/-3.0 micromol/g muscle/30 min) was significantly (P < .05) lower than that in the control (20.2+/-2.4 or 23.0+/-3.1 micromol/g muscle/30 min) and pioglitazone (17.8+/-2.4 or 20.7+/-2.0 micromol/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-fructose-fed insulin-resistant rats.
为研究噻唑烷二酮类口服抗糖尿病药物吡格列酮对胰岛素抵抗状态下葡萄糖及胰岛素代谢的影响，对高糖喂养大鼠进行了肝脏及后肢灌注研究。将雄性Wistar白化大鼠随机分为以下几组，每组喂养2周：(1) 正常饲料组（对照组）；(2) 高糖饲料组（高糖组）；(3) 高糖饲料加吡格列酮组（吡格列酮摄入量约为10 mg/kg体重；吡格列酮组）。吡格列酮给药可使高糖组大鼠血浆胰岛素、甘油三酯及游离脂肪酸（FFA）水平恢复正常。在灌注肝脏中，果糖组（57.1±9.1 μmol/g肝脏/20分钟）和吡格列酮组（44.7±10.1 μmol/g肝脏/20分钟）中胰高血糖素诱导的葡萄糖输出增加量显著高于对照组（27.6±5.7 μmol/g肝脏/20分钟）（P<0.01）。吡格列酮组的该水平显著低于果糖组（P<0.05）。在存在100或500 μU/mL胰岛素的情况下，果糖组中胰岛素介导的胰高血糖素诱导的葡萄糖输出减少量（29.8±7.8或38.9±9.3 μmol/g肝脏/20分钟）显著低于对照组（45.8±14.2或54.5±8.5 μmol/g肝脏/20分钟）和吡格列酮组（44.4±9.2或56.2±10.8 μmol/g肝脏/20分钟）（P均<0.05）。在灌注后肢中，果糖组的葡萄糖摄取量（8.2±2.0 μmol/g肌肉/30分钟）显著低于对照组（12.1±2.3 μmol/g肌肉/30分钟）和吡格列酮组（11.8±3.1 μmol/g肌肉/30分钟）（P<0.05）。在存在100或500 μU/mL胰岛素的情况下，果糖组的葡萄糖摄取量（12.0±5.2或17.4±3.0 μmol/g肌肉/30分钟）显著低于对照组（20.2±2.4或23.0±3.1 μmol/g肌肉/30分钟）和吡格列酮组（17.8±2.4或20.7±2.0 μmol/g肌肉/30分钟）（P均<0.05）。对照组、果糖组和吡格列酮组肝脏及后肢的胰岛素摄取无显著差异。这些结果表明，吡格列酮可改善高糖喂养的胰岛素抵抗大鼠中胰高血糖素诱导的肝脏葡萄糖输出增加，并降低胰岛素诱导的肌肉葡萄糖摄取，而不改变胰岛素摄取。
