Submitted on May 29, 2002
Accepted on May 11, 2003
Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport
Hua Ai1, Evelyn Ralston2, Hans P.M.M. Lauritzen3, Henrik Galbo4, and Thorkil Ploug3*
1 Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; Institute of Sports Medicine, The Third Hospital, Peking University, Peking, China
2 Light Imaging Section, NIAMS, National Institutes of Health, Bethesda, MD, USA
3 Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
4 Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: tp{at}mfi.ku.dk.
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 are 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 3 different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for up to 8h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport nor 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 the soleus muscle but not in FDB 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.
