INS and Hyperglycemia: The main role in the development of a deficiency of NGFin diabetes is known to be its reduced formation from the proNGF precursor as aresult of hyperglycemia-induced oxidative stress [44, 45], whichsuppresses protease activity and shifts the proNGF/NGF ratio towards theprecursor prevalence that promotes apoptosis of insulin-secreting cells,contrary to mature NGF, exerting an antiapoptotic effect(Fig. 3).