Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage

Oxidative stress also plays an important role in the pathogenesis of diabetic neuropathy (DN). Both resveratrol (RES) and exercise (EX) have potent anti-oxidative benefits. Low levels of nerve growth factor (NGF) and SIRT1 (a member of sirtuin family) have been reported in patients with DN. The current study has been designed to investigate the role of serum NGF and SIRT1 on DN-induced hyperalgesia and motor incoordination and to evaluate the possible protective role of RES and/or EX. A total of 40 male adult albino rats divided into five groups; control, DN, DN + RES, DN + EX, and DN + RES and EX. DN was confirmed by sensorimotor disturbance and diminished nerve conduction velocity (NCV). NGF and SIRT1 levels were measured by western blot. Calcitonin gene-related peptide (CGRP) was measured by PCR. Myofibrillar degeneration and inflammation scores were revealed via H&E microscopic analysis of the gastrocnemius muscle. Immunohistochemical evaluation of caspase3 and TNF-α was performed in the lumber segment of spinal cord and gastrocnemius muscle sections. Ultrastructural evaluation of sciatic nerve axonal degeneration has also been assessed. DN group showed decreased SIRT1 level, decreased NGF level and correlated with CGRP level and Na+/K+ ATPase. Treatment with RES and/or EX resulted in improvement of sensorimotor disturbance. DN characterized by reduced SOD level, whereas RES and/or EX could limit oxidative damage by up-regulation Bcl2, Akt and GAP-43 and down-regulation of caspase3 and TNF-α. In conclusion, increased level of SIRT1and NGF by incorporation of RES (natural supplementation) and EX (life style modification) could improve the neuroinflammatory state in DN.