L. Bertimattera et al., AN ALDOSE REDUCTASE INHIBITOR BUT NOT MYOINOSITOL BLOCKS ENHANCED POLYPHOSPHOINOSITIDE TURNOVER IN PERIPHERAL-NERVE FROM DIABETIC RATS, Metabolism, clinical and experimental, 45(3), 1996, pp. 320-327
Experimental diabetic neuropathy, whether chemically induced or presen
t 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 polyphosphoinositi
des, particularly phosphatidylinositol-4,5-bisphosphate (PIP2). This s
tudy examined the relationship of these alterations by assessing the e
ffects of myo-inositol and the aldose reductase inhibitor, sorbinil, s
upplied as dietary supplements, on sorbitol and myo-inositol concentra
tions and incorporation of P-32 into polyphosphoinositides in sciatic
nerve from rats killed 8 weeks after induction of diabetes with strept
ozotocin. Nerves from diabetic rats killed after 8 weeks of disease ex
hibited 52% to 76% greater PIP2 labeling, markedly elevated sorbitol l
evels, 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 stand
ard rat chow beginning immediately after induction of diabetes, remain
ed substantially elevated, whereas myo-inositol levels were corrected
to normal. Essentially the same results were obtained when rats were f
ed the myo-inositol-containing diet beginning 4 weeks after streptozot
ocin injection. In contrast, PIP2 labeling in nerves from diabetic rat
s that received the sorbinil supplemented diet for either 4 or 8 weeks
was not different from that in controls. myo-Inositol levels in these
animals were also restored to normal, whereas sorbitol levels remaine
d elevated, albeit reduced by approximately 30%. These results indicat
e that myo-inositol administration is unable to completely counteract
the impact of diabetes on the turnover of monoesterified phosphate gro
ups in PIP2. In contrast, sorbinil can correct this abnormality, but t
his beneficial effect is not dependent on the presence of normal sorbi
tol concentrations. Copyright (C) 1996 by W.B. Saunders Company