[Perspective for the treatment of diabetic neuropathy: translation from molecular studies to bedside].
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 alpha-isoform expression and the increase in vessel PKC activity was due to membrane beta-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.
Yagihashi
Soroku
S
Department of Pathology, Hirosaki University School of Medicine.
Yamagishi
Shin-ichiro
S
Wada
Ryuichi
R
D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D003929:Diabetic Neuropathies / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D010525:Peripheral Nerves / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D011108:Polymers; C024617:polyol; D000449:Aldehyde Reductase; D011493:Protein Kinase C; C030704:magnesium sodium potassium ATPase; D000254:Sodium-Potassium-Exchanging ATPase