The aetiology of neuropathy in experimental diabetes

Abstract

Most information on the aetiology of experimental diabetic neuropathy comes from studies on rodent models, particularly the streptozotocin-diabetic rat. The major factor that impairs small and large nerve fibre function is a decrease in nerve and ganglion perfusion. This leads to reduced conduction velocity, increased resistance to ischaemic conduction failure, blunted regenerative capacity, painful neuropathy, and autonomic nerve dysfunction. Hyperglycaemia, altered lipid metabolism and reduced insulin action combine to cause adverse metabolic effects on vasa nervorum, vascular endothelium being a notable target. The resultant reduced vasodilation and increased vasoconstriction causes endoneurial hypoxia. Oxidative stress is of primary importance, due to increased production of reactive oxygen species from a plethora of intra- and extracellular sources. Advanced glycation and carbonyl stress play a supporting role, as does essential fatty acid dysmetabolism. These mechanisms are associated with alterations in cell signalling mediated by protein kinases, nuclear factor Kappa B and poly (ADP-ribose) polymerase.