Nerve conduction velocity and axonal transport of 6-phosphofructokinase activity in galactose-fed rats.
This study examined sciatic motor nerve conduction velocity (MNCV) and the accumulation of 6-phosphofructokinase (PFK) activity proximal and distal to a sciatic nerve ligature in rats fed a diet containing 20% galactose for 4 weeks. MNCV was reduced in the galactose-fed rats to 94% of controls, (P less than 0.05) but PFK activity accumulations were not different from those in controls. Daily administration of the aldose reductase inhibitor ponalrestat throughout the study to another group of galactose-fed rats prevented dulcitol accumulation, myo-inositol depletion and increased water content of the sciatic nerve seen in galactose-fed rats. This effective aldose reductase inhibition also prevented the reduced MNCV and had no effect on accumulations of PFK activity. These data support earlier work suggesting that deficits in the axonal transport of PFK activity in diabetic rats are unrelated to either exaggerated flux through the polyol pathway, polyol accumulation or ischemic hypoxia and indicate the possible need for the elucidation of other pathogenic mechanisms which may contribute to the development of diabetic neuropathy.
Willars
G B
GB
Department of Pharmacology, School of Pharmacy, University of London, U.K.
Calcutt
N A
NA
Tomlinson
D R
DR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism; D004032:Diet; D004594:Electrophysiology; D004376:Galactitol / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology; D007294:Inositol / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology*; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010793:Phthalazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology
D001786:Blood Glucose; D010793:Phthalazines; D004376:Galactitol; C042829:ponalrestat; D007294:Inositol; D000449:Aldehyde Reductase; D010732:Phosphofructokinase-1; D005690:Galactose