Palmitate induced insulin resistance by PKCtheta-dependent activation of mTOR/S6K pathway in C2C12 myotubes.
The underlying mechanism of palmitate-induced insulin resistance in skeletal muscle cells is obscure. In this study, we showed that palmitate inhibited the insulin signaling in C2C12 myotubes, accompanied with the enhanced phosphorylation of protein kinase C-theta (PKCΘ). The inhibitory effects of palmitate on the insulin signaling were diminished in PKCΘ- and mTOR (mammalian target of rapamycin)-deficient C2C12 myotubes, and C2C12 myotubes pre-treated with rapamycin. In addition, the phosphorylation of mTOR and p70 ribosomal S6 kinase (S6K) enhanced by palmitate was attenuated in PKCΘ-deficient C2C12 myotubes and in C2C12 myotubes treated with PKCΘ pseudosubstrate. Taken together, our results suggested that palmitate-induced insulin resistance in C2C12 myotubes is mediated by PKCΘ/mTOR/S6K pathway.
Wang
X
X
Department of Pathophysiology, Yunyang Medical College, Shiyan, China.
Yu
W
W
Nawaz
A
A
Guan
F
F
Sun
S
S
Wang
C
C
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007333:Insulin Resistance; D007527:Isoenzymes / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D000074121:Protein Kinase C-theta; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D007527:Isoenzymes; D019308:Palmitic Acid; C546843:mTOR protein, mouse; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta