Leptin Treatment and Skeletal Muscle Insulin Resistance

瘦素治疗和骨骼肌胰岛素抵抗

• 批准号: 6314602
• 负责人: BEN B YASPELKIS
• 金额: $ 14.21万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6314602
• 关键词: diabetes mellitus therapy; glucose tolerance; glucose transport; glucose transporter; glycogen; hormone regulation /control mechanism; insulin; insulin sensitivity /resistance; laboratory rat; leptin; muscle pharmacology; nonhuman therapy evaluation; noninsulin dependent diabetes mellitus; obesity; phosphatidylinositol 3 kinase; striated muscles; western blottings

DESCRIPTION: (Scanned from the applicant's abstract) It is well documented that obesity is associated with resistance to insulin-stimulated glucose uptake and may ultimately lead to the development of non-insulin-dependent diabetes. As over 80 percent of insulin-stimulated glucose clearance is mediated by skeletal muscle, it is of importance to evaluate interventions that may improve insulin action in skeletal muscle. Recently, leptin, the product of the ob gene, has been shown to reduce fat mass, hyperglycemia and hyperinsulinemia. Of particular interest, chronic leptin administration increases insulin-stimulated glucose uptake and transport in normal rat skeletal muscle. However, it is unknown if chronic leptin administration improves insulin-stimulated glucose uptake and transport in insulin-resistant skeletal muscle. Therefore, the aims of the present investigation are to determine whether chronic leptin administration improves whole body glucose tolerance in an insulin-resistant rodent model, whether chronic leptin administration improves insulin-stimulated skeletal muscle glucose uptake and transport in insulin-resistant skeletal muscle and whether the improvements in leptin-treatment insulin-resistant skeletal muscle result from alterations in enzymatic activity, glycogen concentration and/or GLUT4 protein. Additionally, it will be determined if chronic leptin administration alters the subcellular distribution of GLUT4, insulin-stimulated translocation of the GLUT4 protein and if improvements in leptin-treatment Insulin-resistant skeletal muscle may also result from alterations in insulin stimulated IRS-1-associated P1 3-klnase activity.

描述：（从申请人的摘要中扫描）有据可查的是 肥胖与对胰岛素刺激的葡萄糖摄取的抵抗有关 最终可能导致非胰岛素依赖型糖尿病的发生。作为 超过 80% 的胰岛素刺激葡萄糖清除是由骨骼介导的 肌肉，评估可能改善胰岛素的干预措施非常重要 骨骼肌中的作用。最近，ob基因的产物瘦素（leptin） 已被证明可以减少脂肪量、高血糖和高胰岛素血症。的 特别感兴趣的是，长期使用瘦素会增加胰岛素刺激 正常大鼠骨骼肌中葡萄糖的摄取和转运。然而，它是 未知长期施用瘦素是否可以改善胰岛素刺激的血糖 胰岛素抵抗骨骼肌的摄取和转运。因此，目标 本研究的目的是确定慢性瘦素是否 给药可改善胰岛素抵抗患者的全身葡萄糖耐量 啮齿动物模型，长期施用瘦素是否改善胰岛素刺激 胰岛素抵抗骨骼中骨骼肌葡萄糖的摄取和转运 肌肉以及瘦素治疗的改善是否会产生胰岛素抵抗 骨骼肌是酶活性、糖原改变的结果 浓度和/或 GLUT4 蛋白。此外，还将确定是否 长期使用瘦素会改变 GLUT4 的亚细胞分布， 胰岛素刺激的 GLUT4 蛋白易位以及如果改善 瘦素治疗 骨骼肌胰岛素抵抗也可能是由于 胰岛素的改变刺激了 IRS-1 相关的 P1 3-激酶活性。