title: Troglitazone induces GLUT4 translocation in L6 myotubes.
abstract: A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2, and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yonemitsu
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Shintani
authors.forename: R
authors.initials: R
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Hosoda
authors.forename: G
authors.initials: G
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
chemical_list: D002839:Chromans; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D003513:Cycloheximide; D003847:Deoxyglucose; C089946:2,4-thiazolidinedione; D000077288:Troglitazone