Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle
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Author
Toyoda, Taro
Didesch, Michelle M.
Lee, Min-Young
Sleeman, Mark W.
Musi, Nicolas
Hirshman, Michael F.
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https://doi.org/10.1038/ncomms2851Metadata
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Koh, Ho-Jin, Taro Toyoda, Michelle M. Didesch, Min-Young Lee, Mark W. Sleeman, Rohit N. Kulkarni, Nicolas Musi, Michael F. Hirshman, and Laurie J. Goodyear. 2013. “Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle.” Nature communications 4 (1): 1871. doi:10.1038/ncomms2851. http://dx.doi.org/10.1038/ncomms2851.Abstract
Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707125/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717574
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