Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy.
Nerve myo-inositol depletion, which has been implicated in the pathogenesis of acute experimental diabetic neuropathy, can be reproduced in normal rats by feeding diets enriched in L-fucose, a competitive inhibitor of sodium-dependent myo-inositol transport. Previously, we reported that L-fucose feeding for 6 weeks reproduces the effect of experimental diabetes on nerve Na+-K+-ATPase activity and conduction velocity, which can be prevented by simultaneous dietary myo-inositol supplementation. To further validate this model of myo-inositol depletion, we examined the effects of long-term (24-week) L-fucose feeding and dietary myo-inositol supplementation on nerve Na+-K+-ATPase, nerve conduction 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 associated 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 swelling (P < 0.001), and paranodal demyelination (P < 0.005), without increasing Wallerian degeneration or nerve fiber loss, a pattern qualitatively similar to that seen in early murine diabetic neuropathy. Dietary myo-inositol supplementation prevented these structural changes and increased nodal remyelination, supporting a role of myo-inositol depletion in the genesis of early diabetic neuropathy. The L-fucose model system may therefore serve as an experimental tool to elucidate the pathophysiological role of isolated myo-inositol depletion and its consequences in the multifactorial pathogenesis of diabetic neuropathy.
Sima
A A
AA
Department of Pathology, Wayne State University, Detroit, Michigan 48236, USA.
Dunlap
J A
JA
Davidson
E P
EP
Wiese
T J
TJ
Lightle
R L
RL
Greene
D A
DA
Yorek
M A
MA
D000818:Animals; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000517:prevention & control*; D005643:Fucose / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007294:Inositol / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D009431:Neural Conduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013497:Sural Nerve / Q000473:pathology
D005643:Fucose; D007294:Inositol; D000254:Sodium-Potassium-Exchanging ATPase