Changes in skeletal muscle contractile properties in streptozocin-induced diabetic rats and role of polyol pathway and hypoinsulinemia.
Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect on strength performance assessed by maximal tetanic tension production. Treatment with the aldose reductase inhibitor ponalrestat largely prevented relaxation defects but had little effect on contraction. For the fast muscle, twitch times were relatively unaffected, but maximum tetanic relaxation rate was reduced. In addition, tetanic tension output decreased. These changes were largely prevented by ponalrestat treatment. The effects of partial insulin therapy were also investigated. This regimen reduced hypoinsulinemia, but sufficient hyperglycemia remained to stimulate the polyol pathway. It prevented the slowing of soleus twitch contraction but had no effect on relaxation. For extensor digitorum longus, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate, which were antagonized by ponalrestat. A 1% dietary myo-inositol supplement had little effect on contractile function in slow or fast muscles. It was concluded that polyol-pathway activity is an important factor underlying skeletal muscle functional changes in diabetes, probably acting through disruption of Ca2+ handling. Hypoinsulinemia was considered a secondary factor causing atrophy, particularly of fast muscles. There was no evidence of effects dependent on neuropathy.
Cameron
N E
NE
Department of Physiology, University of Aberdeen, United Kingdom.
Cotter
M A
MA
Robertson
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004032:Diet; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007294:Inositol / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation; D009132:Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D010793:Phthalazines / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010793:Phthalazines; C042829:ponalrestat; D007294:Inositol; D000449:Aldehyde Reductase