Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle

• DOI: 10.1038/nutd.2013.13
• Publication Date: 2013-06-10T15:35:52Z
• Authors: R J W Middelbeek; M A Chambers; P Tantiwong; J T Treebak; D An; M F Hirshman; N Musi; L J Goodyear
• Keywords: GLUT4; Glucose clamp technique

Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 TBC1D1 is critical for GLUT4 translocation facilitating uptake, but their regulation in human not well understood.Here, lean, obese T2D subjects underwent a euglycemic-hyperinsulinemic clamp, vastus lateralis biopsies were obtained before, at 30 180 min post infusion.Obese had higher body mass indexes fasting concentrations, showed resistance. Consistent clamp findings, insulin-stimulated Thr(642), site previously to be important uptake rodents. Interestingly, Thr(590), regulated by rodents, was only increased subjects, although functional significance this difference unknown.These data show differentially regulates muscle. Impaired accompanied dysregulation muscle, suggesting these may regulate humans.