INSR and Insulin resistance: It was reported that TNF-α can activate protein kinase C-α (PKC-α), which inhibits the insulin receptor (INSR)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1), determining the inhibition of the phosphoinositide 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt)/GLUT4 signalling and, consequently, the induction of insulin resistance and the development of T2DM [26].