{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:46:48Z","timestamp":1787017608286,"version":"build-2736575974"},"reference-count":28,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:p>\n                    Kv1.3 is a voltage-gated K\n                    <jats:sup>+<\/jats:sup>\n                    channel expressed in insulin-sensitive tissues. We previously showed that gene inactivation or pharmacological inhibition of Kv1.3 channel activity increased peripheral insulin sensitivity independently of body weight by augmenting the amount of GLUT4 at the plasma membrane. In the present study, we further examined the effect Kv1.3 on GLUT4 trafficking and tested whether it occurred via an insulin-dependent pathway. We found that Kv1.3 inhibition by margatoxin (MgTX) stimulated glucose uptake in adipose tissue and skeletal muscle and that the effect of MgTX on glucose transport was additive to that of insulin. Furthermore, whereas the increase in uptake was wortmannin insensitive, it was completely inhibited by dantrolene, a blocker of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release from intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores. In white adipocytes in primary culture, channel inhibition by Psora-4 increased GLUT4 translocation to the plasma membrane. In these cells, GLUT4 protein translocation was unaffected by the addition of wortmannin but was significantly inhibited by dantrolene. Channel inhibition depolarized the membrane voltage and led to sustained, dantrolene-sensitive oscillations in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration. These results indicate that the apparent increase in insulin sensitivity observed in association with inhibition of Kv1.3 channel activity is mediated by an increase in GLUT4 protein at the plasma membrane, which occurs largely through a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent process.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00091.2005","type":"journal-article","created":{"date-parts":[[2006,1,10]],"date-time":"2006-01-10T19:57:46Z","timestamp":1136923066000},"page":"C345-C351","source":"Crossref","is-referenced-by-count":59,"title":["Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma membrane via a Ca\n                    <sup>2+<\/sup>\n                    -dependent mechanism"],"prefix":"10.1152","volume":"290","author":[{"given":"Yanyan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peili","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary V.","family":"Desir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Berger J\n                      , Hayes N, Szalkowski DM, and Zhang B.\n                      PI 3-kinase activation is required for insulin stimulation of glucose transport into L6 myotubes.\n                      Biochem Biophys Res Commun\n                      205\n                      : 570\u2013576, 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and Chandy KG.\n                      Molecular properties and physiological roles of ion channels in the immune system.\n                      J Clin Immunol\n                      21\n                      : 235\u2013252, 2001.","DOI":"10.1023\/A:1010958907271"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Coderre L\n                      , Kandror KV, Vallega G, and Pilch PF.\n                      Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.\n                      J Biol Chem\n                      270\n                      : 27584\u201327588, 1995.","DOI":"10.1074\/jbc.270.46.27584"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Etgen GJ Jr\n                      , Wilson CM, Jensen J, Cushman SW, and Ivy JL.\n                      Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat.\n                      Am J Physiol Endocrinol Metab\n                 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1999.","DOI":"10.1152\/ajpcell.1999.277.4.C701"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Hayashi T\n                      , Wojtaszewski JFP, and Goodyear LJ.\n                      Exercise regulation of glucose transport in skeletal muscle.\n                      Am J Physiol Endocrinol Metab\n                      273\n                      : E1039\u2013E1051, 1997.","DOI":"10.1152\/ajpendo.1997.273.6.E1039"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Litherland GJ\n                      , Hajduch E, and Hundal HS.\n                      Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues.\n                      Mol Membr Biol\n                      18\n                      : 195\u2013204, 2001.","DOI":"10.1080\/09687680110076407"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Mahaut-Smith MP\n                      , Hussain JF, and Mason MJ.\n                      Depolarization-evoked Ca\n       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X, Barth P, Busch AE, Schlottmann K, Pongs O, and Lang F.\n                      Tyrosine phosphorylation-dependent suppression of a voltage-gated K\n                      +\n                      channel in T lymphocytes upon Fas stimulation.\n                      J Biol Chem\n                      271\n                      : 20465\u201320469, 1996.","DOI":"10.1074\/jbc.271.34.20465"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Thorell A\n                      , Hirshman MF, Nygren J, Jorfeldt L, Wojtaszewski JFP, Dufresne SD, Horton ES, Ljungqvist O, and Goodyear LJ.\n                      Exercise and insulin cause GLUT-4 translocation in human skeletal muscle.\n                      Am J Physiol Endocrinol Metab\n                      277\n                      : E733\u2013E741, 1999.","DOI":"10.1152\/ajpendo.1999.277.4.E733"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Vennekamp J\n                      , Wulff H, Beeton C, Calabresi PA, Grissmer S, 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