Caveolopathies - insulin resistance, lipid metablism

小窝是维持完整性、运输和信号转导的特化细胞膜结构域。在肌肉中，小窝结构和功能的重要蛋白质是小窝蛋白3和cavin 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敲除小鼠具有胰岛素抗性，骨骼肌中葡萄糖摄取减少，表现出葡萄糖耐量受损，并且具有增加的血清脂质。Cav-3也是β2-肾上腺素能受体的结合伴侣，表明在儿茶酚胺诱导的脂解中起重要作用。我们将在体内和体外研究胰岛素信号和脂质代谢在小窝蛋白病中的作用。

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.