Peripheral diabetic neuropathy (PDN) is one of the most devastating complications of diabetes mellitus. The pathogenesis of PDN involves hyperglycemia-initiated mechanisms as well as other factors, i.e., impaired insulin signaling, hypertension, disturbances of fatty acid and lipid metabolism. This review describes new findings in animal and cell culture models:

1. Supporting the importance of previously established hyperglycemia-initiated mechanisms, such as increased aldose reductase activity, nonenzymatic glycation/glycoxidation, activation of protein kinase-C, and enhanced oxidative stress;

2. Addressing the role of nitrosative stress and downstream effectors of oxidative-nitrosative injury, such as poly(ADP-ribose) polymerase activation, mitogen-activated protein kinase activation, cyclooxygenase-2 activation, activation of nuclear factor-KB, and impaired Ca2+ homeostasis and signaling; and

3. Suggesting the contribution of two newly discovered mechanisms, such as 12/15-lipoxygenase activation and Na+/H+-exchanger-1 activation, in PDN.

Key Words: Aldose reductase; calcium signaling; cyclooxygenase-2; diabetic neuropathy; 12/15-lipoxygenase; mitogen-activated protein kinases; nuclear factor-KB; nonenzymatic glycation; oxidative-nitrosative stress; protein kinase-C; poly(ADP-ribose) polymerase.

Diabetes Sustenance

Diabetes Sustenance

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