MUSCLE GLUCOSE METABOLISM IN DIABETES AND EXERCISE

描述（改编自申请人的申请）：肌肉GLUT 4发挥 在维持葡萄糖稳态中起重要作用， GLUT 4蛋白的增加导致葡萄糖处置的实质性变化。 因此，GLUT4基因是治疗干预的合理靶点。 NIDDM。 目前，运动是唯一可以增加 GLUT4基因的表达。 运动可以提高 GLUT4基因，但GLUT4蛋白的增加甚至大于 GLUT4 mRNA的增加。 因此，据信， 运动增加GLUT4的转录和翻译速率， 增加肌肉中葡萄糖转运和改善葡萄糖耐量。 在这 研究人员提出实验来研究 导致GLUT4葡萄糖转运蛋白增加的机制 对锻炼的反应。 为了解释转录率的增加 运动后，我们的假设，肌肉收缩"激活"一个 转录因子结合到"运动反应元件（ERE）"， GLUT4启动子并激活GLUT4基因的转录。 到 研究这一假设，他们将建立GLUT4基因的区域， 含有运动反应元件（ERE），确定DNA 然后使用该序列来分离和表征 由运动激活的转录因子。 自从增加 GLUT4蛋白在运动训练中的反应大于 GLUT4 mRNA的增加，似乎有可能是一个额外的 在信息翻译或 GLUT4蛋白的降解。 已经确定， GLUT4 mRNA的两种剪接变体，我们的假设是，运动 选择性地增加GLUT 4剪接变体， は自动的 这将通过测量翻译率进行调查 而对照组中GLUT4 mRNA的两种剪接变体的肌肉水平 并锻炼训练过的老鼠肌肉。

DESCRIPTION (Adapted from the applicant's application): Muscle GLUT4 plays an important role in maintaining glucose homeostasis and relatively small increases of GLUT4 protein lead to substantial changes in glucose disposal. Thus, the GLUT4 gene is a rational target for intervention for the treatment of NIDDM. At present exercise is the only means available for increasing expression of the GLUT4 gene. Exercise increases the transcription rate of the GLUT4 gene, but the increase in GLUT4 protein is even greater than can be accounted for by the increase in GLUT4 mRNA. Thus, it is believed that exercise increases both the transcription and translation rates of GLUT4 to increase glucose transport in muscle and improve glucose tolerance. In this grant application the investigators propose experiments to investigate the mechanism that bring about the increase in GLUT4 glucose transport protein in response to exercise. To explain the increased rate of transcription after exercise our hypothesis that muscle contraction "activates" a transcription factor that binds to an "exercise response element (ERE)" in the GLUT4 promoter and activates transcription of the GLUT4 gene. To investigate this hypothesis they will establish the region of the GLUT4 gene that contains the exercise response element (ERE), determine the DNA sequence of the ERE and then use that sequence to isolate and characterize the transcription factor that is activated by exercise. Since the increase in GLUT4 protein in response to exercise training is greater than the increase in GLUT4 mRNA, it seems likely that there is an additional adaptation to exercise at the level of either translation of the message or in the degradation of GLUT4 protein. It has been established that there are two splice variants of the GLUT4 mRNA and our hypothesis is that exercise selectively increases the GLUT4 splice variant which is more readily translated. This will be investigated by measuring the rates of translation and the muscle levels of the two splice variants of GLUT4 mRNA in control and exercised trained rat muscle.