Dietary Fat Mitochondria and Insulin Signaling

膳食脂肪线粒体和胰岛素信号传导

• 批准号: 7155943
• 负责人: Chad R. Hancock
• 金额: $ 4.6万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155943
• 关键词: body composition; body physical activity; cellular respiration; dietary lipid; disease /disorder etiology; enzyme substrate; fatty acids; glucose metabolism; hormone regulation /control mechanism; insulin; insulin sensitivity /resistance; laboratory rat; mitochondria; muscle contraction; muscle metabolism; noninsulin dependent diabetes mellitus; nutrition related tag; obesity; oxidation; phosphorylation; postdoctoral investigator; serine threonine protein kinase; striated muscles

DESCRIPTION (provided by applicant): Skeletal muscle plays an integral role in the regulation of the circulating glucose concentration. Thus, the mechanism for skeletal muscle insulin resistance is of great importance for the understanding of the pathogenesis of type-2 diabetes. While a great deal of research has been done on determining what causes skeletal muscle insulin resistance, the mechanism remains unclear. Recent work has suggested that reduced mitochondrial content and/or function in skeletal muscle contributes to insulin resistance and may in fact be genetically determined. It is our hypothesis that the reduction in muscle mitochondria is due to physical inactivity and plays no role in modulating muscle insulin resistance. The primary goal of this study determine the effect of a high fat diet that causes visceral obesity and insulin resistance on skeletal muscle content and functional mitochondria in rats. A second goal is to determine whether insulin stimulated phospohorylation of Akt substrate 160 is impaired in response to high fat feeding.

描述（由申请人提供）：骨骼肌在循环葡萄糖浓度的调节中起着不可或缺的作用。因此，研究骨骼肌胰岛素抵抗的机制对了解2型糖尿病的发病机制具有重要意义。虽然大量的研究已经确定了导致骨骼肌胰岛素抵抗的原因，但其机制仍不清楚。最近的研究表明，骨骼肌中线粒体含量和/或功能的减少有助于胰岛素抵抗，实际上可能是由遗传决定的。我们的假设是，肌肉线粒体的减少是由于缺乏运动，在调节肌肉胰岛素抵抗中没有作用。本研究的主要目的是确定引起内脏肥胖和胰岛素抵抗的高脂肪饮食对大鼠骨骼肌含量和功能性线粒体的影响。第二个目标是确定胰岛素刺激的Akt底物160磷酸化是否在高脂肪喂养时受损。