Muurling Martin, Mensink Ronald P, Pijl Hanno, Romijn Johannes A, Havekes Louis M, Voshol Peter J
TNO-Prevention and Health, Gaubius Laboratory, Leiden, The Netherland.
Metabolism. 2003 Aug;52(8):1078-83. doi: 10.1016/s0026-0495(03)00109-4.
The present study was performed to examine the effects of rosiglitazone treatment on tissue-specific insulin sensitivity. Therefore, we used obese, insulin-resistant ob/ob mice and measured the effects of rosiglitazone treatment on insulin sensitivity and simultaneously tissue-specific uptake of glucose and free fatty acids (FFA) under hyperinsulinemic euglycemic clamp conditions. Rosiglitazone treatment resulted in significantly higher body weight and decreased plasma levels of glucose, insulin, and triglyceride (TG). Glucose tolerance, as well as insulin sensitivity, was improved upon rosiglitazone treatment, as assessed by glucose tolerance and insulin sensitivity tests. Hyperinsulinemic euglycemic clamps showed increased glucose infusion rates with increased whole body insulin sensitivity. Rosiglitazone treatment resulted in increased glucose uptake by cardiac and skeletal muscle under hyperinsulinemic euglycemic clamp conditions, while no differences were observed in FA uptake. Measurement of TG content showed that rosiglitazone treatment resulted in decreased TG content of cardiac muscle, but increased TG content of skeletal muscle. We conclude that rosiglitazone treatment leads to strong improvement of insulin sensitivity, irrespective of increased muscle TG content, in ob/ob mice.
本研究旨在探讨罗格列酮治疗对组织特异性胰岛素敏感性的影响。因此，我们使用肥胖、胰岛素抵抗的ob/ob小鼠，并在高胰岛素正常血糖钳夹条件下，测量罗格列酮治疗对胰岛素敏感性以及同时对组织特异性葡萄糖和游离脂肪酸（FFA）摄取的影响。罗格列酮治疗导致体重显著增加，同时血糖、胰岛素和甘油三酯（TG）的血浆水平降低。通过葡萄糖耐量和胰岛素敏感性测试评估，罗格列酮治疗后葡萄糖耐量以及胰岛素敏感性均得到改善。高胰岛素正常血糖钳夹显示，随着全身胰岛素敏感性增加，葡萄糖输注率升高。在高胰岛素正常血糖钳夹条件下，罗格列酮治疗导致心脏和骨骼肌的葡萄糖摄取增加，而在脂肪酸摄取方面未观察到差异。TG含量测量显示，罗格列酮治疗导致心肌TG含量降低，但骨骼肌TG含量增加。我们得出结论，在ob/ob小鼠中，无论肌肉TG含量增加与否，罗格列酮治疗均可显著改善胰岛素敏感性。
