Caveolin is a major protein component of caveolae, which are the flask-shaped plasma membrane invaginations that accommodate various molecules involved in cellular signaling. Caveolin has been shown to inhibit the function of molecules accumulated within caveolae, such as kinases involved in cell growth and proliferation. According to recent studies, insulin signaling is positively regulated by caveolin and is an exception to the common “anchoring and tranquilizing” concept of caveolin. It has been reported that caveolin either directly or indirectly stimulates the insulin receptor kinase, and the loss of caveolin function causes the disorders of glucose metabolism. In addition, compartmentalization of the insulin receptor and the other molecules within specific cholesterol-rich membrane microdomains called caveolae/lipid rafts also have important roles in regulating insulin signaling. This review focuses on the role of caveolin or caveolae/lipid rafts in insulin signaling and glucose metabolism. Better under-standing these mechanisms should therefore facilitate the development of new therapeutic strategies to control glucose homeostasis and to treat diabetes mellitus.
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