SUPPLEMENTAL MYOINOSITOL PREVENTS L-FUCOSE-INDUCED DIABETIC NEUROPATHY

Nerve myo-inositol depletion, which has been implicated in the pathoge nesis of acute experimental diabetic neuropathy, can be reproduced in normal rats by feeding diets enriched in L-fucose, a competitive inhib itor of sodium-dependent myo-inositol transport. Previously, we report ed that L-fucose feeding for 6 weeks reproduces the effect of experime ntal diabetes on nerve Na+-K+-ATPase activity and conduction velocity, which can be prevented by simultaneous dietary myo-inositol supplemen tation. To further validate this model of myo-inositol depletion, we e xamined the effects of long-term (24-week) L-fucose feeding and dietar y myo-inositol supplementation on nerve Na+-K+-ATPase, nerve conductio n velocity, and myelinated nerve fiber pathology. After 24 weeks of L- fucose enriched (10 or 20%) diets, nerve myo-inositol levels and Na+-K +-ATPase activity decreased significantly (P < 0.05) and were associat ed with a 25-30% reduction in nerve conduction velocity, all of which were completely prevented by 1% dietary myo-inositol. Twenty percent L -fucose diet resulted in significant axonal atrophy, paranodal swellin g (P < 0.001), and paranodal demyelination (P < 0.005), without increa sing Wallerian degeneration or nerve fiber loss, a pattern qualitative ly similar to that seen in early murine diabetic neuropathy. Dietary m yo-inositol supplementation prevented these structural changes and inc reased nodal remyelination, supporting a role of myo-inositol depletio n in the genesis of early diabetic neuropathy. The L-fucose model syst em may therefore serve as an experimental tool to elucidate the pathop hysiological role of isolated myo-inositol depletion and its consequen ces in the multifactorial pathogenesis of diabetic neuropathy.