INS and Hyperglycemia: Experimental data have demonstrated that similar with that in retinal endothelial cells, hyperglycemia environment incudes increased tumor necrosis factor (TNF)-α and suppressors of cytokine-signaling 3 (SOCS3) levels, which subsequently inhabit insulin signaling through the phosphorylation of IRS-1Ser307, a key component of insulin signaling transduction (39).