INS and type 2 diabetes mellitus: Despite the fact that the decrease of insulin and IGF-1 levels in the brain makes a significant contribution to reduction of the activity of insulin/IGF-1 signaling systems in T2DM and MS, the key role is given to abnormalities in these systems caused by oxidative stress, lipotoxicity and increased production of proinflammatory and proapoptotic factors [16,83–86].