Caveolopathies - insulin resistance, lipid metablism

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。

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.