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Figure 3. Role of MG in the development of insulin resistance. MG modifies the arginine residue on B-chain of insulin molecule, which causes its conformational change and leads to dysfunction of insulin. MG-insulin adducts reduce Glc uptake in insulin targeted cells, including adipocytes and skeletal muscle cells, causing an increase in blood Glc. However, the formation of MG-insulin adducts decreases insulin clearance through liver cells and impairs feedback inhibition on insulin release from pancreatic ß-cells. Moreover, MG might modify proteins to form advanced glycation products (AGEs) and alter the generation of reactive oxygen species and reactive nitrogen species (RNS), which damage vascular tissue and cause high blood pressure. Therefore, a chronic increase in the circulating MG concentration, with enhanced formation of MG-insulin adducts and AGEs might contribute to hyperglycemia, hyperinsulinemia, and hypertension in insulin-resistance syndrome.
