AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1

By N. Wu, B. Zheng, A. Shaywitz, Y. Dagon, Christine M Tower, G. Bellinger, Che-Hung Shen, Jennifer Wen, J. Asara, T. McGraw and 2 more. Molecules and Cells, 2013

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Summary TXNIP is an α-arrestin family protein that is induced in response to glucose elevation. It has been shown to provide a negative feedback loop to regulate glucose uptake into cells, though the biochemical mechanism of action has been obscure. Here, we report that TXNIP suppresses glucose uptake directly by binding to the glucose transporter, Glut1, inducing Glut1 internalization through clathrin coated pits, as well as indirectly by reducing the level of Glut1 mRNA. In addition, we show that energy stress results in phosphorylation of TXNIP by AMP-dependent protein kinase (AMPK), leading to its rapid degradation. This suppression of TXNIP results in an acute increase in Glut1 function and an increase in Glut1 mRNA (hence total protein levels) for long-term adaptation. The glucose influx through GLUT1 restores ATP/ADP ratios in the short run and ultimately induces TXNIP protein production to suppress glucose uptake once energy homeostasis is reestablished.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f303d8aeead0055ee1ca14a8147e4caab66d1857