Glycolysis and diabetes mellitus

Type 2 diabetes (T2DM) is a chronic metabolic disease characterized by insulin resistance and impaired insulin secretion. Insulin resistance is often present in early metabolic dysregulation stages like obesity/overweight and metabolic syndrome, leading to hyperinsulinemia and β-cell overstimulation. Progressive β-cell exhaustion leads to hyperglycemia and T2DM establishment, creating a metabolic overload on the other cells. Glucose uptake in cells like myocytes and adipocyte is insulin-dependent, but other cells like neurons, glial cells, endothelial cells, podocytes, and so forth are insulin-independent and uptake glucose upon their concentration raise in plasma. Thus chronic hyperglycemia creates a metabolic challenge for such cells, which have to deal with increased metabolic flux through the glycolytic pathway. This excessive glycolytic flux induces the activation of several pathways that contribute to oxidative stress, protein modification, matrix stiffness, and apoptosis and ultimately to the vascular and neurological complications of T2DM. This chapter summarizes the main pathways involved in such processes.