Lee M K, Olefsky J M
Department of Medicine, School of Medicine, University of California, San Diego, USA.
Metabolism. 1995 Sep;44(9):1166-9. doi: 10.1016/0026-0495(95)90010-1.
Troglitazone is a newly developed antidiabetic agent that shows hypoglycemic effects in insulin-resistant animal models and non-insulin-dependent diabetic humans. To determine whether this drug could affect in vivo insulin action acutely, insulin-stimulated glucose utilization was measured with the euglycemic glucose clamp technique before, during, and after troglitazone infusion (20 micrograms/min) in normal rats. Hepatic glucose production (HGP) was measured with a tracer-dilution technique (D-[3-3H]-glucose). At 18-pmol/kg/min insulin infusion rate, steady-state glucose disposal rate (GDR) was significantly increased during troglitazone infusion versus control vehicle infusion (162 +/- 6.1 v 142.3 +/- 4.4 mumol/kg/min, P < .02). The glucose infusion rate (GIR) required to maintain euglycemia increased shortly (10 to 20 minutes) after initiation of troglitazone infusion and was significantly greater until 30 minutes after cessation of the drug versus the vehicle infusion. At 9-pmol/kg/min insulin infusion rate, HGP was significantly decreased during troglitazone infusion as compared with control vehicle infusion (21.7 +/- 3.5 v 39.5 +/- 3.7 mumol/kg/min, P < .02). These results indicate that troglitazone can acutely increase in vivo insulin action in normal rats, and some possible mechanisms are discussed.
曲格列酮是一种新开发的抗糖尿病药物，在胰岛素抵抗动物模型和非胰岛素依赖型糖尿病患者中显示出降血糖作用。为了确定该药物是否能急性影响体内胰岛素作用，在正常大鼠中，在输注曲格列酮（20微克/分钟）之前、期间和之后，采用正常血糖葡萄糖钳夹技术测量胰岛素刺激的葡萄糖利用情况。用示踪剂稀释技术（D-[3-3H]-葡萄糖）测量肝葡萄糖生成（HGP）。在胰岛素输注速率为18皮摩尔/千克/分钟时，与对照载体输注相比，输注曲格列酮期间稳态葡萄糖处置率（GDR）显著增加（162±6.1对142.3±4.4微摩尔/千克/分钟，P<.02）。开始输注曲格列酮后不久（10至20分钟），维持正常血糖所需的葡萄糖输注速率（GIR）增加，并且在停止药物输注后30分钟内显著高于载体输注。在胰岛素输注速率为9皮摩尔/千克/分钟时，与对照载体输注相比，输注曲格列酮期间HGP显著降低（21.7±3.5对39.5±3.7微摩尔/千克/分钟，P<.02）。这些结果表明，曲格列酮可急性增加正常大鼠体内的胰岛素作用，并对一些可能的机制进行了讨论。
