Diabetes, Vol 46, Issue 2 301-306, Copyright © 1997 by American Diabetes Association

ARTICLES

Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy

AA Sima, JA Dunlap, EP Davidson, TJ Wiese, RL Lightle, DA Greene and MA Yorek
Department of Pathology, Wayne State University, Detroit, Michigan 48236, USA.

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. G. Obrosova, P. Pacher, C. Szabo, Z. Zsengeller, H. Hirooka, M. J. Stevens, and M. A. Yorek Aldose Reductase Inhibition Counteracts Oxidative-Nitrosative Stress and Poly(ADP-Ribose) Polymerase Activation in Tissue Sites for Diabetes Complications Diabetes, January 1, 2005; 54(1): 234 - 242. [Abstract] [Full Text] [PDF]

				J. H. Jin and A. Seyfang High-affinity myo-inositol transport in Candida albicans: substrate specificity and pharmacology Microbiology, December 1, 2003; 149(12): 3371 - 3381. [Abstract] [Full Text] [PDF]

				M. J. Coady, B. Wallendorff, D. G. Gagnon, and J.-Y. Lapointe Identification of a Novel Na+/myo-Inositol Cotransporter J. Biol. Chem., September 13, 2002; 277(38): 35219 - 35224. [Abstract] [Full Text] [PDF]

				P. L. Smith, J. T. Myers, C. E. Rogers, L. Zhou, B. Petryniak, D. J. Becker, J. W. Homeister, and J. B. Lowe Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus J. Cell Biol., August 19, 2002; 158(4): 801 - 815. [Abstract] [Full Text] [PDF]

				Z. Jiang, S. K. Chung, C. Zhou, P. R. Cammarata, and S. S. M. Chung Overexpression of Na+-Dependent Myo-inositol Transporter Gene in Mouse Lens Led to Congenital Cataract Invest. Ophthalmol. Vis. Sci., May 1, 2000; 41(6): 1467 - 1472. [Abstract] [Full Text]