Study of Insulin resistance involving impaired GLUT4 translocation

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Defective insulin-responsive GLUT4 translocation is the earliest detectable feature of insulin resistance. Biochemical and nanometrological analyses herein revealed that sortilin, a member of the Vps10p-family sorting receptor, plays a critical role in establishing trans-Golgi network system specialized for generating the insulin-responsive GLUT4-strage vesicles that emerged to be severely deranged under certain insulin resistant conditions. This study thereby unmasks that insulin resistance is caused by not only defects in insulin signaling but also impairment of GLUT4 trafficking itself (“sorting disorder").