Diabetic enteric neuropathy: imbalance between oxidative and antioxidative mechanisms

Abstract Enteric neurons located in different intestinal regions display different susceptibilities to diabetic damage and insulin treatment, highlighting the importance of the neuronal microenvironment in the pathogenesis of diabetic neuropathy. Shifts in the balance between the production and scavenging of free radicals lead to segment-specific oxidative stress in the gut, which in turn contribute to regional pathological environment and enteric neuropathy in diabetes. Both the accumulation of reactive oxygen species and the activation of endogenous antioxidants show distinct regional differences in diabetes. Based on these, the distal part of the small intestine shows greater changes to oxidative stress than the proximal part. Nitrergic myenteric neurons that contain heme oxygenase enjoy higher protection, while those that do not contain heme oxygenase are heavily affected by oxidative damage. Moreover, microbial dysbiosis demonstrated in the distal part of the gut may contribute to inducing endogenous heme oxygenase defense mechanisms in the ileum and colon.