Regulation of muscle glucose transport and GLUT-4 by nerve-derived factors and activity-related processes.
Glucose transport and GLUT-4 were examined in muscles in which activity and nerve-derived factors were eliminated (denervation) and in muscles in which only muscle activity was eliminated but in which nerve-derived factors were maintained [tetrodotoxin (TTX) treatment]. After 3 days of denervation, insulin-stimulated 3-O-methylglucose transport was markedly lowered in perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius; < or = 35%). GLUT-4 was also decreased by 11-65% in denervated muscles. Blocking muscle activity with TTX superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated glucose transport to the same extent as in the denervated muscles (P > 0.05). However, in soleus, plantaris, and red gastrocnemius muscles, GLUT-4 expression was reduced much less by TTX treatment than by denervation (P < 0.05). GLUT-4 mRNA abundance was decreased in denervated muscles but not in TTX-treated muscles. These results suggest that muscle activity largely regulates the insulin-signaling mechanisms of glucose transport and that nerve-derived trophic factors affect pretranslational events to regulate GLUT-4 expression.
Megeney
L A
LA
Department of Kinesiology, University of Waterloo, Ontario, Canada.
Michel
R N
RN
Boudreau
C S
CS
Fernando
P K
PK
Prasad
M
M
Tan
M H
MH
Bonen
A
A
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003714:Denervation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D009124:Muscle Proteins; D009132:Muscles / Q000294:innervation / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D051275:Glucose Transporter Type 4; D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D013779:Tetrodotoxin; D005947:Glucose