Maegawa H, Tachikawa-Ide R, Ugi S, Iwanishi M, Egawa K, Kikkawa R, Shigeta Y, Kashiwagi A
Third Department of Medicine, Shiga University of Medical Science, Japan.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1078-82. doi: 10.1006/bbrc.1993.2588.
A new oral agent, pioglitazone, increases insulin sensitivity by activating receptor kinase in insulin-resistant rats. To clarify the mechanism, we studied in vitro effects of glucose and pioglitazone on the insulin receptor function using Rat 1 fibroblasts which expressed human insulin receptors. Insulin receptor kinase activity was impaired by incubating cells for 4 days in the presence of 27mM D-glucose. The glucose effect was time- and dose-dependent and also specific for D-glucose, since D-raffinose incubation had no effect. Pioglitazone treatment did not have any effect on intact receptor kinase. However, exposure of both 27mM D-glucose and 0.1 microM pioglitazone to the cells completely prevented the glucose-induced impairment of insulin receptor kinase activity, suggesting that pioglitazone might reverse the processes which are critical for the glucose-induced desensitization of insulin receptor kinase.
一种新型口服药物吡格列酮，可通过激活胰岛素抵抗大鼠的受体激酶来提高胰岛素敏感性。为阐明其机制，我们使用表达人胰岛素受体的大鼠成纤维细胞系（Rat 1）研究了葡萄糖和吡格列酮对胰岛素受体功能的体外作用。在27mM D -葡萄糖存在的情况下将细胞培养4天，胰岛素受体激酶活性受损。葡萄糖的这种作用具有时间和剂量依赖性，并且对D -葡萄糖具有特异性，因为D -棉子糖孵育没有影响。吡格列酮处理对完整的受体激酶没有任何影响。然而，将27mM D -葡萄糖和0.1μM吡格列酮同时作用于细胞，可完全防止葡萄糖诱导的胰岛素受体激酶活性受损，这表明吡格列酮可能逆转了对葡萄糖诱导的胰岛素受体激酶脱敏至关重要的过程。
