Caveolopathies - insulin resistance, lipid metablism

凹陷病 - 胰岛素抵抗、脂质代谢

• 批准号: 47222957
• 负责人: Dr. Michael Boschmann
• 金额: --
• 依托单位: Center for Cardiovascular Research (CCM)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/47222957?language=en
• 关键词: Caveolopathies; insulin; resistance; lipid; metablism

Caveolae are specialized cell-membrane domains that maintain integrity, trafficking, and signal transduction. In muscle, important proteins for caveolar structure and function are caveolin 3 and cavin1/ptrf. Patients lacking caveolae have rippling muscle, muscular dystrophy, lipodystrophy and cardiac conduction defects. Cav-3 knockout mice are insulin resistant, have decreased glucose uptake in skeletal muscle, exhibit impaired glucose tolerance, and have increased serum lipids. Cav-3 is also a binding partner of the β2- adrenergic receptor, suggesting an important role in catecholamine-induced lipolysis. None of these features have been studied comprehensively in man. We will study the role of insulin signaling and lipid metabolism in caveolinopathies in vivo and in vitro.

小窝是特殊的细胞膜域，维持完整性、运输和信号转导。在肌肉中，对小窝结构和功能重要的蛋白质是小窝蛋白3和小窝蛋白1/ptrf。缺乏小窝的患者有波纹肌、肌营养不良、脂肪营养不良和心脏传导缺陷。CAV-3基因敲除小鼠具有胰岛素抵抗，骨骼肌葡萄糖摄取减少，表现出糖耐量受损，并增加了血脂。β-3也是CAV-2-肾上腺素能受体的结合伙伴，提示其在儿茶酚胺诱导的脂解中起重要作用。这些特征在人类身上都没有得到全面的研究。我们将在体内和体外研究胰岛素信号和脂代谢在小凹疾病中的作用。