Polyol pathway-related skeletal muscle contractile and morphological abnormalities in diabetic rats.
This study examined the effect of inhibition of aldose reductase, the first enzyme in the polyol pathway, on fast and slow twitch skeletal muscle morphology and function in streptozotocin-induced diabetes in rats. There was a preventative investigation with diabetes duration of 4 months, and a reversal investigation where treatment was given for 2 months following an untreated period of 2 months. For slow twitch soleus muscle, contractions were prolonged by diabetes, and this was partially prevented but not reversed by treatment. Relaxation was profoundly slowed, and both prevention and reversal ameliorated the changes. Diabetes had minimal effects on tension production for soleus. However, for fast twitch extensor digitorum longus, although there was little effect on speed-related contractile parameters, tetanic tension production was progressively reduced with diabetes duration. This effect was antagonized by treatment. Soleus fatigue resistance was markedly reduced by diabetes, but restored to normal by treatment. There was a reduction in oxidative enzyme staining (succinic dehydrogenase), and capillary-fibre ratio, both of which were ameliorated by aldose reductase inhibition. Mean soleus fibre area was reduced after 4 months of diabetes, and this was prevented but not reversed by treatment. Fibre area was also reduced in extensor digitorum longus, particularly for fast glycolytic fibres. There was a small amelioration with treatment. It is concluded that enhanced polyol pathway activity makes a contribution to diabetic myopathy, and that aldose reductase inhibitors can prevent this by actions on muscle fibres and their vascular supply.
Cotter
M A
MA
Department of Biomedical Sciences, Marischal College, University of Aberdeen.
Cameron
N E
NE
Robertson
S
S
Ewing
I
I
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000517:prevention & control; D010793:Phthalazines / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000378:metabolism
D010793:Phthalazines; D011108:Polymers; C024617:polyol; C042829:ponalrestat; D000449:Aldehyde Reductase; D013385:Succinate Dehydrogenase