An aldose reductase inhibitor but not myo-inositol blocks enhanced polyphosphoinositide turnover in peripheral nerve from diabetic rats

Metabolism: Clinical and Experimental
L Berti-MatteraJ Eichberg

Abstract

Experimental diabetic neuropathy, whether chemically induced or present in several spontaneously diabetic animal models, is characterized by sorbitol accumulation and myo-inositol depletion and usually also by enhanced turnover of the monoesterified moieties of polyphosphoinositides, particularly phosphatidylinositol-4,5-bisphosphate (PIP2). This study examined the relationship of these alterations by assessing the effects of myo-inositol and the aldose reductase inhibitor, sorbinil, supplied as dietary supplements, on sorbitol and myo-inositol concentrations and incorporation of 32P into polyphosphoinositides in sciatic nerve from rats killed 8 weeks after induction of diabetes with streptozotocin. Nerves from diabetic rats killed after 8 weeks of disease exhibited 52% to 76% greater PIP2 labeling, markedly elevated sorbitol levels, and 30% less myo-inositol when compared with age-matched normal rats. Incorporation of isotope into PIP2 in nerves from animals fed a myo-inositol supplement, added to either a high-sucrose diet or standard rat chow beginning immediately after induction of diabetes, remained substantially elevated, whereas myo-inositol levels were corrected to normal. Essentially the same results were obtained when...Continue Reading

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Citations

Aug 8, 1998·Progress in Retinal and Eye Research·M J Crabbe, D Goode
Mar 22, 2005·The Journal of Biological Chemistry·K Sandeep PrabhuC Channa Reddy
Nov 16, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Irina G ObrosovaMartin J Stevens

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