Emerging role of protein S-nitrosylation in diabetes and diabetes-associated diseases.

The global obesity epidemic is worsening in many parts of the world, leading to a gradual increase in the occurrence of metabolic illnesses such as type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Emerging evidence highlights protein S-nitrosylation as a critical regulatory mechanism in diabetes-associated disease. S-nitrosylation, a post-translational redox-based modification that refers to the formation of a covalent bond between nitric oxide and a cysteine residue's reduced thiol, adds an S-nitrosothiol group to substrate proteins. Several recent investigations have shown that dysregulated protein S-nitrosylation contributes significantly to the development of insulin resistance, mitochondrial dysfunction, oxidative stress, inflammation, and ER stress in a wide range of metabolic disorders. In this review, we will describe the dynamic change between protein S-nitrosylation and denitrosylation in the etiology of diabetes and diabetes-associated disease, as well as the levels of S-nitrosylation enzyme activity and modification proteins in these diseases. This will highlight the therapeutic potential of focusing on the enzyme's activity to modify the levels of protein S-nitrosylation, thereby improving our understanding of nitric oxide's function in redox signaling and metabolic diseases.