Orexin-A Stimulates Insulin Secretion Through the Activation of the OX1 Receptor and Mammalian Target of Rapamycin in Rat Insulinoma Cells.

The study aimed to investigate the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in orexin-A/OX1 receptor-induced insulin secretion in rat insulinoma INS-1 cells. Rat insulinoma INS-1 cells were grown and treated with various concentrations of orexin-A, with or without OX1 receptor-selective antagonist SB674042 or the phosphatidylinositol 3-kinase/mTOR antagonist PF-04691502. Insulin release experiments, Western blot analysis, and statistical analysis were conducted using INS-1 cells. Our results showed that treating cells with orexin-A increased the expression of the OX1 receptor and the phosphorylation of mTOR in a concentration-dependent manner. An increase in insulin secretion was also observed for cells treated with orexin-A. We further demonstrated that the increase in insulin secretion was dependent on the activation of the OX1 receptor and mTOR signaling pathway by using the OX1 receptor-selective antagonist SB674042 or the phosphatidylinositol 3-kinase/mTOR antagonist PF-04691502, which abolished the effects of orexin-A treatment. Our results concluded that orexin-A/OX1 receptor stimulates insulin secretion by activating AKT and its downstream target, mTOR. Therefore, orexins may regulate the energy balance for cell survival with the involvement of mTOR in this process.