{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:46:53Z","timestamp":1775108813013,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008222","name":"University of Montpellier","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008222","id-type":"DOI","asserted-by":"crossref"}]},{"name":"technology transfer acceleration company SATT AxLR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Protein inhibitor of neuronal NO synthase (PIN) or dynein light chain 8 (LC8) is a highly conserved protein interacting with multiple partners, like neuronal NO synthase (nNOS) or myosin Va to modulate a variety of cellular functions. As PIN is expressed in skeletal muscle, our aim was to investigate a possible role of PIN in glucose uptake in L6 and primary muscle cells. PIN overexpression resulted into a decrease in glucose uptake with reduced GLUT4 expression and translocation at the plasma membrane, similarly to the pharmacological blockade of nNOS with L-NAME. PIN effect is mediated by a reduction in nNOS protein level and a direct interaction with nNOS leading to a reduced NO production in L6 myocytes. Surprisingly, a siRNA targeting PIN decreased glucose uptake and GLUT4 translocation, suggesting the involvement of nNOS-independent effects. We therefore focused on myosin Va which interacts with PIN in L6 myocytes. Myosin Va silencing provoked a decrease in glucose uptake. As PIN siRNA also reduced myosin Va expression, this confirms the essential role of myosin Va in the observed effects of PIN silencing on glucose uptake. We conclude that PIN modulates glucose uptake and GLUT4 translocation in rat muscle cells, through NO-dependent and -independent mechanisms.<\/jats:p>","DOI":"10.3390\/antiox15040436","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:09:21Z","timestamp":1775038161000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PIN (Protein Inhibitor of Neuronal Nitric Oxide Synthase) Modulates Glucose Uptake Through NO-Dependent and Independent Mechanisms in Rat Muscle Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"J\u00e9r\u00e9my","family":"Leroy","sequence":"first","affiliation":[{"name":"Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0707-8599","authenticated-orcid":false,"given":"Karima","family":"Mezghenna","sequence":"additional","affiliation":[{"name":"Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Tousch","sequence":"additional","affiliation":[{"name":"Qualisud, University of Montpellier, CIRAD, Montpellier SupAgro, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaufret","family":"Canovas","sequence":"additional","affiliation":[{"name":"Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Laune","sequence":"additional","affiliation":[{"name":"Kyomed, 34184 Grabels, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-2909","authenticated-orcid":false,"given":"Martine","family":"Pugni\u00e8re","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM, U1194, University of Montpellier, 34093 Montpellier, France"},{"name":"ICM, Institut R\u00e9gional du Cancer, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9965-9996","authenticated-orcid":false,"given":"Jacqueline","family":"Azay-Milhau","sequence":"additional","affiliation":[{"name":"Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5912-5233","authenticated-orcid":false,"given":"Anne-Dominique","family":"Lajoix","sequence":"additional","affiliation":[{"name":"Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1126\/science.274.5288.774","article-title":"PIN: An associated protein inhibitor of neuronal nitric oxide synthase","volume":"274","author":"Jaffrey","year":"1996","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20929","DOI":"10.1074\/jbc.272.33.20929","article-title":"Dimerization of the highly conserved light chain shared by dynein and myosin V","volume":"272","author":"Benashski","year":"1997","journal-title":"J. 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