Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport

1 Copenhagen Muscle Research Center, Department of Medical Physiology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, and 4 Department of Rheumatology, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark; 2 Institute of Sports Medicine, The Third Hospital, Peking University, 100083 Beijing, China; and 3 Light Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 Submitted 29 May 2002 ; accepted in final form 11 May 2003 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 8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the 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. cytoskeleton; metabolism; signaling; glucose transporter 4; exercise; colchicine; nocodazole Address for reprint requests and other correspondence: T. Ploug, Dept. of Medical Physiology, The Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark (E-mail: tp{at}mfi.ku.dk ).