INS and obesity due to melanocortin 4 receptor deficiency: It has been found that this cytokine is increased in adipose tissue, where its release has been greater in obesity.36 Normally, insulin action requires activation of the substrate of insulin receptor 1 (IRS1), a component that is essential for activating PI3K in response to insulin; this leads to phosphorylation of protein kinase B (also known as AKT), which results in an increase of GLUT4 transporters in the plasma membrane that maintain glucose homeostasis.