The effect of aldose reductase inhibition on the pattern of nerve conduction deficits in diabetic rats.
Conduction deficits caused by 2-4 months diabetes were examined in one sensory and six motor nerve branches of mature rats. The effect of aldose reductase inhibitor (ponalrestat) treatment was assessed in preventative and reversal studies. The efficacy of 1% dietary myoinositol supplementation was also examined in a 2 month preventative group. Diabetes suppressed a maturation-related increase in conduction velocity in the interosseus nerve supplying foot muscles. This was unaffected by any treatment. Large conduction velocity reductions (22-29%) seen for fast nerves supplying four calf muscles and sensory saphenous nerves were prevented by ponalrestat treatment. In a reversal group, which had 2 months of diabetes followed by 2 months of treatment, restoration of conduction varied between nerves, ranging from 100% in sensory saphenous to 25% in soleus motor branches. Myo-inositol supplementation had little effect. Sciatic nerves accumulated the sugar alcohol sorbitol with diabetes. This was markedly reduced by treatment, and correlated with the conduction velocity improvement. There was a 40% reduction in nerve free myo-inositol levels after 2 months diabetes. Ponalrestat normalized myo-inositol in the short term but failed to do so in 4 month preventative and reversal groups. Myo-inositol treatment did not affect nerve levels. The data implicate the polyol pathway in the diabetic conduction velocity deficits seen in normally fast conducting motor and sensory nerves and suggest that aldose reductase inhibitor action does not depend on restoration of nerve myo-inositol levels.
Cameron
N E
NE
Department of Physiology, Marischal College, University of Aberdeen.
Cotter
M A
MA
Robertson
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000294:innervation; D009431:Neural Conduction / Q000187:drug effects*; D010543:Peroneal Nerve / Q000503:physiopathology; D010793:Phthalazines / Q000494:pharmacology* / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D007294:Inositol; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase