Rinsho Shinkeigaku (Clinical Neurology)

The 46th Annual Meeting of the Japanese Society of Neurology

Perspective for the treatment of diabetic neuropathy: translation from molecular studies to bedside

Soroku Yagihashi, M.D., Shin-ichiro Yamagishi, M.D. and Ryuichi Wada, M.D.

Department of Pathology, Hirosaki University School of Medicine

Drastic increase in a population of diabetic patients urges to establish effective treatment or management of peripheral neuropathy, the most common complication of diabetes. Recent studies emphasize the occurrence of peripheral neuropathy in patients with impaired glucose tolerance, which condition is now shown to augment polyol pathway as well as non-enzymatic protein glycation in the peripheral nerve, exerted by postprandial hyperglycemia. Such metabolic cascades in turn result in tissue-specific alterations of cellular signaling, represented by decreased protein kinase C (PKC) activity and Na, K-ATPase activity in the peripheral nerve and contrariwise increased PKC activity in microvessels. The decrease in nerve PKC activity was demonstrated to associate with reduced membrane α-isoform expression and the increase in vessel PKC activity was due to membrane β-isoform expression, respectively. Dual mechanisms of nerve and vascular alterations in addition to multiple metabolic factors may operate in the development of diabetic neuropathy in a complicated manner. Consequently, inhibition of hyperglycemia as well as specific intervention of single molecules related to altered cellular signaling is the essential approach for the primary prevention of diabetic neuropathy.

(CLINICA NEUROL, 45: 966|968, 2005)
key words: diabetic neuropathy, molecular mechanisms, polyol pathway, glycation, oxidative stress

(Received: 27-May-05)