High Fat Diet Alterations in Muscle Insulin Signaling

高脂肪饮食改变肌肉胰岛素信号

• 批准号: 6752630
• 负责人: BEN B YASPELKIS
• 金额: $ 21.15万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752630
• 关键词: SDS polyacrylamide gel electrophoresis; biological signal transduction; carbohydrate metabolism; dietary lipid; glucose tolerance; glucose transport; glucose transporter; hormone regulation /control mechanism; immunoprecipitation; insulin sensitivity /resistance; laboratory rat; metabolism disorder; muscle function; nucleic acid quantitation /detection; nutrition related tag; pathologic process; phosphatidylinositol 3 kinase; striated muscles; western blottings

DESCRIPTION (provided by applicant): To better understand how insulin resistance develops, a variety of models have been utilized. The high fat fed rodent model displays many commonalities to the abdominal obesity syndrome found in insulin resistant adults. However, the basis of skeletal muscle insulin resistance in this model is unclear due to reports that PI 3-kinase activity is decreased, and equivocal if Akt activation, atypical Protein Kinase C phosphorylation, GLUT4 protein concentration and GLUT4 translocation are altered. The insulin signaling cascade and glucose transporter effector system is considerably more complex than what has been previously evaluated and more importantly, the mechanism by which high fat feeding induces these alterations has not been addressed. In addition, while skeletal muscle insulin resistance can be reversed, the basis for these improvements in a high fat fed rodent model have not been fully elucidated. Therefore, the aims of this proposal are to determine: 1) the mechanism of chronic high fat feeding induced skeletal muscle insulin resistance, how the defects are manifested in the insulin signaling cascade and glucose transporter effector system and if the IkB-alpha pathway contributes to the development of skeletal muscle insulin resistance and 2) if those factors associated with high fat feeding-induced skeletal muscle insulin resistance can be corrected or if improvements in insulin-stimulated glucose transport result from a compensatory mechanism. The resolution of these issues has implications for advancing our understanding of how dietary composition induces impairments in carbohydrate metabolism and how skeletal muscle insulin resistance can be corrected.

描述（由申请人提供）：为了更好地理解胰岛素抵抗如何发展，已经使用了多种模型。高脂肪喂养的啮齿动物模型显示出与胰岛素抵抗成年人中发现的腹部肥胖综合征的许多共性。然而，该模型中骨骼肌胰岛素抵抗的基础尚不清楚，因为有报道称 PI 3 激酶活性降低，并且如果 Akt 激活、非典型蛋白激酶 C 磷酸化、GLUT4 蛋白浓度和 GLUT4 易位发生改变则意义不明。胰岛素信号级联和葡萄糖转运效应系统比之前评估的要复杂得多，更重要的是，高脂肪喂养诱导这些改变的机制尚未得到解决。此外，虽然骨骼肌胰岛素抵抗可以逆转，但高脂肪喂养的啮齿动物模型中这些改善的基础尚未完全阐明。因此，本提案的目的是确定：1​​）慢性高脂喂养诱导骨骼肌胰岛素抵抗的机制，胰岛素信号级联和葡萄糖转运效应系统的缺陷如何表现，以及IkB-α途径是否有助于骨骼肌胰岛素抵抗的发展；2) 与高脂肪喂养引起的骨骼肌胰岛素抵抗相关的那些因素是否可以得到纠正，或者胰岛素刺激的葡萄糖转运的改善是否是由补偿机制引起的。 这些问题的解决对于增进我们对饮食成分如何引起碳水化合物代谢损害以及如何纠正骨骼肌胰岛素抵抗具有重要意义。