Importantly, Toll-like receptor 4 (TLR4) is responsible for initiating diabetes by expressing the transcriptional factor nuclear factor-kappaB (NF-κB) and the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to produce ROS, which also induce activation of endothelial nitric oxide synthase (eNOS) and xanthine oxidase enzymes [17]. Here, NOS3 is linked to diabetes mellitus.