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TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab GTPase-activating protein (RabGAP) that has been implicated in regulating GLUT4 trafficking. TBC1D1 can be phosphorylated by the AMP-activated protein kinase (AMPK) on Ser 231 , which consequently interacts with 14-3-3 proteins. Given the key role for AMPK in regulating insulin-independent muscle glucose uptake, we hypothesised that TBC1D1-Ser 231 phosphorylation and/or 14-3-3 binding may mediate AMPK-governed glucose homeostasis.

A Tbc1d1 Ser231Ala-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice