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Nutr Diabetes. 2013 Jun 10;3:e74. doi: 10.1038/nutd.2013.13.

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

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  • 1Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.

Abstract

INTRODUCTION:

Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 translocation facilitating glucose uptake, but their regulation in human skeletal muscle is not well understood.

METHODS:

Here, lean, obese and T2D subjects underwent a euglycemic-hyperinsulinemic clamp, and vastus lateralis muscle biopsies were obtained before, and at 30 and 180 min post insulin infusion.

RESULTS:

Obese and T2D subjects had higher body mass indexes and fasting insulin concentrations, and T2D subjects showed insulin resistance. Consistent with the clamp findings, T2D subjects had impaired insulin-stimulated phosphorylation of AS160 Thr(642), a site previously shown to be important in glucose uptake in rodents. Interestingly, insulin-stimulated phosphorylation of TBC1D1 Thr(590), a site shown to be regulated by insulin in rodents, was only increased in T2D subjects, although the functional significance of this difference is unknown.

CONCLUSION:

These data show that insulin differentially regulates AS160 and TBC1D1 phosphorylation in human skeletal muscle. Impaired insulin-stimulated glucose uptake in T2D subjects is accompanied by dysregulation of AS160 and TBC1D1 phosphorylation in skeletal muscle, suggesting that these proteins may regulate glucose uptake in humans.

PMID:
23752133
[PubMed]
PMCID:
PMC3697402
Free PMC Article
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