Role of JNK1 in Skeletal Muscle Glucose Metabolism

描述(由申请人提供)：体育锻炼对2型糖尿病的发病、进展和严重程度起到有益的作用。然而，关于运动对骨骼肌有益影响的潜在机制，人们知之甚少。最近的研究表明，应激激活的激酶c-Jun-NH2-末端激酶亚型1(JNK1)在调节全身葡萄糖代谢中起着作用。目前尚不清楚JNK1信号的作用是否通过改变骨骼肌糖代谢来实现。这项建议的总体目标是确定JNK1信号对骨骼肌对胰岛素和急性运动的反应的生理后果。具体地说，这项提案中概述的实验将检验JNK1缺乏改变胰岛素和运动调节骨骼肌葡萄糖摄取、糖原合成和参与葡萄糖代谢的细胞内信号蛋白的能力的假设。最终，这些研究将有助于确定2型糖尿病的分子机制，以及体育锻炼对骨骼肌葡萄糖代谢的有益影响。此外，这些研究可能会发现治疗2型糖尿病的新药理靶点。

DESCRIPTION (provided by applicant): Physical exercise exerts a salutary effect on the onset, progression, and severity of type 2 diabetes. However, little is known regarding the mechanisms underlying the beneficial effects of exercise on skeletal muscle. Recent studies have suggested a role for the stress-activated kinase, c-jun-NH2-terminal kinase isoform 1 (JNK1), in the regulation of whole body glucose metabolism. It is currently not known whether the effects of JNK1 signaling are mediated via alterations in glucose metabolism in skeletal muscle. The overall goal of this proposal is to determine the physiological consequences of JNK1 signaling on skeletal muscle responses to insulin and acute bouts of exercise. Specifically, the experiments outlined in this proposal will test the hypothesis that JNK1 deficiency alters the ability of insulin and exercise to regulate skeletal muscle glucose uptake, glycogen synthesis, and intracellular signaling proteins involved in glucose metabolism. Ultimately, these studies will help to define the molecular mechanisms underlying type 2 diabetes and the beneficial effects of physical exercise on skeletal muscle glucose metabolism. Also, these studies may uncover new pharmacological targets for the treatment of type 2 diabetes.