{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:47:40Z","timestamp":1792140460343,"version":"4.4.0"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Lipid oversupply induces insulin resistance in skeletal muscle (SkM), partly by altering mitochondrial function and dynamics. Although electrical pulse stimulation (EPS) improves insulin signaling in myotubes, the mechanisms contributing to this effect under lipotoxic conditions remain unclear. Thus, we investigated whether EPS restores lipid\u2010induced insulin resistance in association with changes in mitochondrial respiration and dynamics, lipotoxic intermediates and evaluated the contribution of contraction\u2010induced secreted factors, including small extracellular vesicles (sEV). Murine C2C12 myotubes were treated with palmitate (PA, 0.3\u2009mmol\/l) and subjected to EPS (1\u2009Hz, 11.5\u2009V) for 24\u2009h. Insulin signaling, mitochondrial dynamics, respiratory capacity and lipotoxic intermediates were assessed by Western blotting, high\u2010resolution respirometry and liquid chromatography\u2010tandem mass spectrometry in control (CON) and PA\u2010treated cells before and after EPS. Additionally, CON and PA\u2010treated cells were incubated for 24\u2009h with conditioned media and sEV from unstimulated or EPS\u2010stimulated CON and PA\u2010treated cells to evaluate the effect of the myocellular secretome on AKT signaling. PA reduced insulin\u2010stimulated AKT(Ser473) and (Thr308) phosphorylation, which was partially rescued by EPS. In PA cells, EPS decreased the fusion proteins mitofusin 1 and 2 (MFN1, MFN2) and increased the fission marker dynamin\u2010related protein 1 (DRP1). However, mitochondrial respiration and lipid accumulation were unaffected by EPS. Furthermore, conditioned media and sEV from EPS\u2010stimulated cells enhanced AKT phosphorylation in PA\u2010treated cells. These findings demonstrate that attenuation of lipid\u2010induced insulin resistance is independent of mitochondrial respiratory capacity and lipid accumulation, but it is associated with alterations in proteins involved in mitochondrial dynamics and is likely mediated by exercise\u2010derived sEV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.70240","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:36:45Z","timestamp":1791293805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electrical Pulse Stimulation Partially Restores Insulin Signaling in Palmitate\u2010Induced Insulin\u2010Resistant Skeletal Muscle Cells via Mitochondrial Remodeling and Contractile Activity\u2010Dependent Secretome"],"prefix":"10.1002","volume":"241","author":[{"given":"Falcone","family":"Alessandro","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8610-1192","authenticated-orcid":false,"given":"Yilmaz","family":"Sevgican","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendlinger","family":"Mona","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-847X","authenticated-orcid":false,"given":"Schrauwen","family":"Patrick","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-8323","authenticated-orcid":false,"given":"Lipaeva","family":"Polina","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piribauer","family":"Marlene","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0737-8172","authenticated-orcid":false,"given":"Heilmann","family":"Geronimo","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1419-7177","authenticated-orcid":false,"given":"Trenkamp","family":"Sandra","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Roden","family":"Michael","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"},{"name":"Department of Endocrinology and Diabetology, Medical Faculty and University Hospital D\u00fcsseldorf Heinrich\u2010Heine\u2010University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-6636","authenticated-orcid":false,"given":"Mastrototaro","family":"Lucia","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"German Center for Diabetes Research (DZD e.V.) Partner D\u00fcsseldorf Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284386"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi9551"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154803"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00467.2022"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2419-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05128-1"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.01.06.db05-1286"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00756.2009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3395-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.092031"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1387"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00641-2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13763"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1559556"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq4461"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1549316"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.90880.2008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2019-0208"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R067595"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2018.11.009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156361"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0519"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05335-w"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705070104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05603-11"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/642038"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2851"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071715-050656"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160736"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002580"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2454-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010286200"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00921.2011"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-08-0591"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105471"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154892"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202300078"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05430-6"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47843-y"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.11.012"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00123.2017"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12830"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70045"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.08.010"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP276990"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.02.002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr8849"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1832"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.21.7794-7808.2003"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030277"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00311.2024"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1797-8"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-106293"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00405.2023"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05596-z"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001256"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2017.170"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-9910"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801917R"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-060721-095517"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3540359"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406499200"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409229111"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.12.016"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.08.002"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/402175"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.70240","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.70240","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.70240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:35:10Z","timestamp":1792139710000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.70240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":67,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jcp.70240"],"URL":"https:\/\/doi.org\/10.1002\/jcp.70240","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70240"}}