The role of nitric oxide in diabetic skin (patho)physiology

•NO plays an important role in skin (patho)physiology.•Skin disorders in diabetic conditions involve redox state disturbances.•Fine setting of NO/О2− ratio shows therapeutic potential for diabetic skin. The role of nitric oxide (NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired NO signaling has an important consequence in skin pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between NO and superoxide (О2−). This review describes possible therapeutic significance of different redox state modulators in the treatment of diabetic skin disorders. The focus is on those modulators that tightly control NO/О2− ratio through the complex mechanisms affecting endogenous NO and О2− producing and removing systems. The fact that classic antioxidants failed to show significant benefits in diabetes, emphasizes the importance of such redox mechanism-based and targeted approaches.