title: Calphostin C is an inhibitor of contraction, but not insulin-stimulated glucose transport, in skeletal muscle.
abstract: Wortmannin selectively impairs insulin-stimulated glucose transport in skeletal muscle. To search for an inhibitor specific for contraction-stimulated glucose transport, we screened a number of calmodulin and PKC inhibitors for their ability to impair contraction- and insulin-stimulated 2-deoxyglucose uptake in incubated rat soleus muscles. In concentrations that did not reduce contraction-induced force output, among calmodulin inhibitors W-7 inhibited both contraction- and insulin-stimulated glucose transport by up to 50% (P < 0.05), while Calmidazolium impaired only insulin-stimulated glucose transport (P < 0.05), and Trifluoperazine and Phenoxybenzamine did not influence glucose transport. In concentrations that did not reduce force generation, among PKC inhibitors Calphostin C specifically inhibited contraction-stimulated glucose transport (P < 0.05), whereas insulin-stimulated transport was impaired by Rottlerin and Bisindolylmaleimide I (P < 0.05), and both contraction- and insulin-stimulated glucose transport were inhibited by RO-31-8220 (P < 0.05). Calphostin C did not reduce contraction-induced increase in AMP-activated protein kinase (AMPK) activity. In conclusion, we have identified specific inhibitors of both contraction- and insulin-stimulated glucose transport. Both calmodulin and different isoenzymes of the PKC family may be involved in contraction- and insulin-stimulated glucose transport. Calphostin C does not influence glucose transport during contractions via stimulation of AMPK. Calphostin C may be used to unravel signal transduction in contraction-stimulated glucose transport.
authors.affiliation: Copenhagen Muscle Research Center, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Ihlemann
authors.forename: H
authors.initials: H
authors.lastname: Galbo
authors.forename: T
authors.initials: T
authors.lastname: Ploug
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009281:Naphthalenes; C058819:calphostin C; D005947:Glucose