Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport.
Insulin and muscle contractions stimulate glucose transport in skeletal muscle through a translocation of intracellular GLUT4 glucose transporters to the cell surface. Judged by immunofluorescence microscopy, part of the GLUT4 storage sites is associated with the extensive microtubule cytoskeleton found in all muscle fibers. Here, we test whether microtubules are required mediators of the effect of insulin and contractions. In three different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for < or =8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the approximately 30% decrease in insulin-stimulated transport that specifically developed during 8 h of incubation in soleus muscle but not in flexor digitorum brevis or epitrochlearis muscles. In contrast, nocodazole, another microtubule-disrupting drug, rapidly and dose dependently blocked insulin- and contraction-stimulated glucose transport. A similar discrepancy between colchicine and nocodazole was also found in their ability to block glucose transport in muscle giant "ghost" vesicles. This suggests that the ability of insulin and contractions to stimulate glucose transport in muscle does not require an intact microtubule network and that nocodazole inhibits glucose transport independently of its microtubule-disrupting effect.
Ai
Hua
H
Copenhagen Muscle Research Center, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Ralston
Evelyn
E
Lauritzen
Hans P M M
HP
Galbo
Henrik
H
Ploug
Thorkil
T
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism*; D005552:Forelimb; D051275:Glucose Transporter Type 4; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D009124:Muscle Proteins; D051381:Rats; D013314:Stress, Mechanical
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D003847:Deoxyglucose; D003078:Colchicine