Does galactose feeding provide a valid model of consequences of exaggerated polyol-pathway flux in peripheral nerve in experimental diabetes?
This study was designed to examine the effect of exaggerated polyol-pathway flux on sciatic nerve content of polyols, myo-inositol, and water. Rats with streptozocin-induced diabetes of 3- and 12-wk duration and nondiabetic rats fed for 5 days on a diet containing 20% galactose were employed initially. All three conditions showed marked elevation of nerve polyol content, combined with fructose accumulation in the diabetic rats. Galactose-fed rats showed a significant (P less than .01) increase in nerve water content of approximately 30% (when expressed as water/unit dry wt tissue). Diabetic rats showed no change in nerve water. Both diabetic and galactose-fed rats showed a depletion of nerve free myo-inositol, although the extent of depletion was greater in the latter. All these changes were prevented or attenuated by the aldose reductase inhibitor Statil (ICI 128436). When diabetic rats were fed a 20% galactose diet for 5 days, nerves of 3- but not 12-wk diabetic rats showed marked increases in water content. A more mild degree of galactosemia, induced by 5 or 21 days of feeding a diet containing 10% galactose to nondiabetic rats, provoked an increase in nerve water content associated with polyol levels of a similar order to those seen in diabetes. We do not know why polyol-pathway metabolites cause nerve hyperhydration in galactosemia but not in streptozocin-induced diabetes. Such differences urge caution in the use of galactose feeding to model the consequences of exaggerated polyol-pathway flux in nerve to face questions related to neuronal dysfunction in diabetes.
Willars
G B
GB
Department of Physiology and Pharmacology, Medical School, Queens Medical Centre, Nottingham, United Kingdom.
Lambourne
J E
JE
Tomlinson
D R
DR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001834:Body Water / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D005693:Galactosemias / Q000150:complications / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000378:metabolism*
D001786:Blood Glucose; D007294:Inositol