Özet:

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia and complications that include micro- and macrovascular disease. Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocate to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription. Oxidative stress is the major pathogenic factor in diabetes and is mediated by Nrf2, a master regulator of the antioxidant protection response. This response involves a network of cooperating enzymes involved in drug detoxification and metabolic elimination of prooxidants. NRF2-induced antioxidant metabolic pathways include enzymes for the production, utilization, and regeneration of reduced glutathione (GSH). Nrf2 has been shown to have a protective effect on oxidative, inflammatory, and apoptotic. Keap1/Nrf2 signaling pathway can effectively suppress intracellular ROS overproduction and protect pancreatic β-cells from oxidative stress-induced DNA damage, contributing to the suppression of T1DM development. However, inhibition of the Keap1/Nrf2 signaling pathway significantly promoted the progression of T1DM. Diabetic complications can occur in long-term diabetes due to disturbances in metabolic balance, leading microvascular and macrovascular complication. It has been suggested that NRF2-related epigenetic changes reduce the occurrence and progression of diabetic complications by inhibiting oxidative stress. Various of antioxidant such as Vitamins like A, E, C vitamins, carotenoids, and minerals like zinc, manganese, copper, iron, and selenium are essential for the activity of NRF-2 also the natural antioxidants such as curcumin and flavonoids found in vegetables, fruits, and edible herbs also play an important role in activating the Nrf2 signaling pathway. In this review, we summarize the role of oxidative stress in diabetic pathogenesis and the role of antioxidants in the regulation of NRF-2 in the treatment of diabetic mellitus.

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