抄録
Various factors have been implicated in the pathogenesis of diabetic neuropathy such as oxidative stress, polyol pathway hyperactivity, abnormality of Protein kinase C activities and glycation. These glucose-mediated metabolic abnormalities affect all components of nerve tissue including neurons and Schwann cells. Oxidative stress has been considered as major pathogenesis of diabetic neuropathy. To investigate the effects of glucose and a novel antioxidant, resveratorl, on apotosis, dorsal root ganglion (DRG) neurons were isolated from embryonic Sprague-Dawley rats. High glucose for 24 h significantly increased TUNEL positive staining and this increase was ameliorated by resveratrol. Resveratrol increased antioxidant enzyme, NAD(P)H:quinone oxidoreductase-1 (NQO1) expression. These findings suggest that high glucose induced apotosis in neurons and that resveratrol prevented this apotosis via enhancing antioxidative defense mechanism. C-peptide has been demonstrated to have various physiological activities including insulinomimetic effects and recognized as the pathogenesis of type1 diabetic neuropathy. To investigate the effects of high glucose and C-peptide on proliferation activities, immortalized mouse Schwann (IMS32) cells were cultured with high glucose for 4 weeks. High glucose significantly inhibited [3H]-thimidine uptake. C-peptide ameliorated this decrease. Short incubation with C-peptide for 20 min increased phospho-ERK1/2 expression. These observations suggest that high glucose inhibited proliferation in Schwann cells and beneficial effects of C-peptide may be mediated, at least in part, through an amelioration of Schwann cell growth via activation of MAP kinase. [J Physiol Sci. 2008;58 Suppl:S37]
