L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but has been shown to be increased in diabetic individuals. In cultured mammalian cells, L-fucose is a potent competitive inhibitor of myo-inositol transport. Abnormal myo-inositol metabolism has been proposed to be a factor in the development of diabetic complications. To test the hypothesis that myo-inositol deficiency may be responsible for the electrophysiological and biological defects in diabetic neuropathy, rats were fed a diet containing 10 or 20% L-fucose for a period of 6 wk. After 3 wk, the L-fucose diets in two groups of rats were supplemented with 1% myo-inositol. At the end of the study protocol, motor nerve conduction velocity, sciatic nerve tissue Na+-K+-ATPase activity, and myo-inositol content were determined. These results were compared with those of STZ-induced diabetic rats fed either a normal diet or a diet containing 1% myo-inositol or with those given 450 mg/kg body wt of sorbinil. Serum L-fucose levels were significantly increased in rats fed a diet containing 10 or 20% L-fucose. In comparison, the serum L-fucose levels in the diabetic rats were increased to a lesser extent. Motor nerve conduction velocity was significantly slower in rats fed a 10 or 20% L-fucose diet. Sciatic nerve composite and ouabain-sensitive Na+-K+-ATPase activity and myo-inositol content was also significantly decreased. Supplementation of 1% myo-inositol to the L-fucose-containing diet restored nerve myo-inositol levels and significantly improved Na+-K+-ATPase activity and motor nerve conduction velocity. In diabetic rats, similar changes were prevented by treatment with myo-inositol or sorbinil. These observations suggest that myo-inositol deficiency may be a major factor in the development of neural defects associated with acute diabetic neuropathy.
Reduced Motor Nerve Conduction Velocity and Na+-K+-ATPase Activity in Rats Maintained on L-Fucose Diet: Reversal by myo-Inositol Supplementation
Mark A Yorek, Thomas J Wiese, Eric P Davidson, Joyce A Dunlap, Mark R Stefani, Corinne E Conner, Sarah A Lattimer, Mikiko Kamijo, Douglas A Greene, Anders A F Sima; Reduced Motor Nerve Conduction Velocity and Na+-K+-ATPase Activity in Rats Maintained on L-Fucose Diet: Reversal by myo-Inositol Supplementation. Diabetes 1 October 1993; 42 (10): 1401–1406. https://doi.org/10.2337/diab.42.10.1401
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