MUSCLE GLUCOSE METABOLISM IN DIABETES AND EXERCISE

描述（根据申请人的申请改编）：长期目标 这项研究的目的是了解胰岛素的分子机制 骨骼肌的阻力。 最近的实验表明，蛋白质 激酶C（PKC）可能参与胰岛素分泌中胰岛素信号的减少。 抵抗性肌肉 将胰岛素抵抗肌纤维条与 PKC抑制剂可明显增加胰岛素的反应性。 调查人员 我相信这些数据不仅指出蛋白激酶C可能是导致 肌肉胰岛素抵抗，但表明使用PKC抑制剂可能是 有效的糖尿病药物治疗。 他们假设 胰岛素抵抗是由肌肉脂质升高引起的， PKC的活性，使胰岛素磷酸化和失活 受体的 由于运动可以逆转胰岛素抵抗， 运动降低了PKC的活性，恢复了PKC的活性。 胰岛素受体 为了研究他们的中心假设，他们提出了 具体目标：1。 研究胰岛素的磷酸化 胰岛素抵抗肌肉中的受体; 2. 为了确定哪种蛋白激酶 C亚型在胰岛素抵抗肌肉中被激活; 3. 探讨 转基因小鼠中肌肉蛋白激酶C的过度表达是否会导致 胰岛素受体的磷酸化和胰岛素抵抗; 4. 到 研究改变肌肉脂质对胰岛素受体的影响 激酶和蛋白激酶C活性; 5. 为了研究运动是否 减少肌肉脂质和蛋白激酶C，从而恢复 胰岛素受体。 在体外研究人类肌肉的独特机会 使他们能够研究肥胖症中胰岛素抵抗的原因， NIDDM。 在人体肌肉中的研究补充了平行研究， 胰岛素抵抗肥胖Zucker大鼠的肌肉。 这些模型与 他们开发的技术以及与其他人的合作 他们所建立的实验室，使他们唯一有资格， 为理解造成这一现象的原因做出了重大贡献。 肥胖和NIDDM中胰岛素抵抗。

DESCRIPTION (Adapted from the applicant's application): The long term goal of this research is to understand the molecular mechanism(s) of insulin resistance in skeletal muscle. Very recent experiments suggest that protein kinase C (PKC) may be involved in decreased insulin signaling in insulin resistant muscle. Incubating insulin resistant muscle fiber strips with a PKC inhibitor markedly increased the response to insulin. The investigators believe these data not only point to protein kinase C as a possible cause of muscle insulin resistance but suggest that using PKC inhibitors may well be an effective pharmacological treatment for diabetes. It is their hypothesis that insulin resistance is caused by elevated muscle lipids increasing the activity of a PKC, which phosphorylates and inactivates the insulin receptor. Since exercise reverses insulin resistance, they also believe that PKC activity is reduced by exercise, restoring the activity of the insulin receptor. To investigate their central hypothesis they propose the following specific aims: 1. To investigate phosphorylation of the insulin receptor in insulin resistant muscle; 2. To determine which protein kinase C isoforms are activated in insulin resistant muscle; 3. To investigate whether overexpression of muscle protein kinase C in transgenic mice causes phosphorylation of the insulin receptor and insulin resistance; 4. To investigate the effects of altering muscle lipids on the insulin receptor kinase and protein kinase C activity; 5. To investigate whether exercise reduces muscle lipids and protein kinase C, thus restoring the activity of the insulin receptor. The unique opportunity to study human muscle in vitro allows them to investigate the causes of insulin resistance in obesity and NIDDM. Studies in human muscle are supplemented with parallel studies in muscles of insulin resistant obese Zucker rats. These models, linked with the techniques that they have developed and the collaborations with other laboratories that they have established, makes them uniquely qualified to make a substantial contribution toward an understanding of the causes of insulin resistance in obesity and NIDDM.