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Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle activates mTORC2, enhances glucose metabolism and muscle performance.

Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle activates mTORC2, enhances glucose metabolism and muscle performance.
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Ruiz A, Dror E, Handschin C, Furrer R, Perez-Schindler J, Bachmann C, Treves S, Zorzato F,


Ruiz A, Dror E, Handschin C, Furrer R, Perez-Schindler J, Bachmann C, Treves S, Zorzato F, (click to view)

Ruiz A, Dror E, Handschin C, Furrer R, Perez-Schindler J, Bachmann C, Treves S, Zorzato F,

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Scientific reports 2018 01 128(1) 636 doi 10.1038/s41598-017-18844-3
Abstract

SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C dehydrogenase/ reductase family 7. Here we show that its over-expression in mouse skeletal muscles induces enhanced muscle performance in vivo, which is not related to alterations in excitation-contraction coupling but rather linked to enhanced glucose metabolism. Over-expression of SRP-35 causes increased phosphorylation of AktS473, triggering plasmalemmal targeting of GLUT4 and higher glucose uptake into muscles. SRP-35 signaling involves RARα and RARγ (non-genomic effect), PI3K and mTORC2. We also demonstrate that all-trans retinoic acid, a downstream product of the enzymatic activity of SRP-35, mimics the effect of SRP-35 in skeletal muscle, inducing a synergistic effect with insulin on AKTS473 phosphorylation. These results indicate that SRP-35 affects skeletal muscle metabolism and may represent an important target for the treatment of metabolic diseases.

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