ИСТИНА

Metabolic syndrome is a crucial problem of medicine, which characterized by development of insulin resistance. Under physiological conditions insulin acts via phosphorylation of Akt kinase on Thr-308 but additional phosphorylation of Ser-473 is also required for full activation of Akt. Complete activation of Akt results in a spectrum of physiological effects including translocation of GLUT4 to cell membrane. In our work we studied influence of classic inductors of insulin resistance on insulin-dependent Akt phosphorylation of Akt kinase in 3T3L1 adipocytes. We stimulated insulin resistance by treatment of 3T3L1 adipocytes with free fatty acid (FFA) or hydrogen peroxide (H2O2). We have shown that the exposure of GLUT4 on adipocyte's membrane was decreased after treatment by FFA or H2O2 compared to non-treated adipocytes. Also phosphorylation of IRS-1 on Ser-307 was increased after treatment of adipocytes by FFA or H2O2. We analyzed level of pAkt-Thr308 and pAkt-Ser473. We found that in insulin resistant adipocytes pAkt-Thr308 decreased while pAkt-Ser473 increased, in contrast to normal cells. We hypothesized that FFA can activate classic IKK/NF-kB inflammatory pathway. In addition, oxidative stress is also known to promote inflammation. Decline of Thr-308 phosphorylation under inflammatory conditions may occur due to regulatory/inhibitory Ser/Thr phosphorylation of IRS-1. Proposed mechanism of pAkt-Ser473 increase in inflammatory conditions may be associated with IKK-dependent activation of mTORC2. Our data suggest, that IKK may act as a key regulator of insulin signaling, which maintain equivalent Akt phosphorylation on Thr308 and Ser473. This study was supported by RFBR grant #13-04-02014