{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:15:10Z","timestamp":1787163310012,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Postgrado (VRIP) Universidad Aut\u00f3noma de Chile","award":["DIUA 264-2023"],"award-info":[{"award-number":["DIUA 264-2023"]}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Postgrado (VRIP) Universidad Aut\u00f3noma de Chile","award":["1231523"],"award-info":[{"award-number":["1231523"]}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Postgrado (VRIP) Universidad Aut\u00f3noma de Chile","award":["P09-022"],"award-info":[{"award-number":["P09-022"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico (FONDECYT)","award":["DIUA 264-2023"],"award-info":[{"award-number":["DIUA 264-2023"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico (FONDECYT)","award":["1231523"],"award-info":[{"award-number":["1231523"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico (FONDECYT)","award":["P09-022"],"award-info":[{"award-number":["P09-022"]}]},{"name":"ICM-ANID","award":["DIUA 264-2023"],"award-info":[{"award-number":["DIUA 264-2023"]}]},{"name":"ICM-ANID","award":["1231523"],"award-info":[{"award-number":["1231523"]}]},{"name":"ICM-ANID","award":["P09-022"],"award-info":[{"award-number":["P09-022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Individuals with diabetes mellitus present a skeletal muscle myopathy characterized by atrophy. However, the mechanism underlying this muscular alteration remains elusive, which makes it difficult to design a rational treatment that could avoid the negative consequences in muscles due to diabetes. In the present work, the atrophy of skeletal myofibers from streptozotocin-induced diabetic rats was prevented with boldine, suggesting that non-selective channels inhibited by this alkaloid are involved in this process, as has previously shown for other muscular pathologies. Accordingly, we found a relevant increase in sarcolemma permeability of skeletal myofibers of diabetic animals in vivo and in vitro due to de novo expression of functional connexin hemichannels (Cx HCs) containing connexins (Cxs) 39, 43, and 45. These cells also expressed P2X7 receptors, and their inhibition in vitro drastically reduced sarcolemma permeability, suggesting their participation in the activation of Cx HCs. Notably, sarcolemma permeability of skeletal myofibers was prevented by boldine treatment that blocks Cx43 and Cx45 HCs, and now we demonstrated that it also blocks P2X7 receptors. In addition, the skeletal muscle alterations described above were not observed in diabetic mice with myofibers deficient in Cx43\/Cx45 expression. Moreover, murine myofibers cultured for 24 h in high glucose presented a drastic increase in sarcolemma permeability and levels of NLRP3, a molecular member of the inflammasome, a response that was also prevented by boldine, suggesting that, in addition to the systemic inflammatory response found in diabetes, high glucose can promote the expression of functional Cx HCs and activation of the inflammasome in skeletal myofibers. Therefore, Cx43 and Cx45 HCs play a critical role in myofiber degeneration, and boldine could be considered a potential therapeutic agent to treat muscular complications due to diabetes.<\/jats:p>","DOI":"10.3390\/biom13040708","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T04:48:11Z","timestamp":1682052491000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Skeletal Muscle Atrophy Induced by Diabetes Is Mediated by Non-Selective Channels and Prevented by Boldine"],"prefix":"10.3390","volume":"13","author":[{"given":"Luis A.","family":"Cea","sequence":"first","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Av. Llano Subercaseaux 2801, San Miguel, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"V\u00e1squez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Hern\u00e1ndez-Salinas","sequence":"additional","affiliation":[{"name":"Centro de Fisiolog\u00eda Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo, Santiago 7610000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra Z.","family":"Vielma","sequence":"additional","affiliation":[{"name":"Escuela de Odontolog\u00eda, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-408X","authenticated-orcid":false,"given":"Mario","family":"Castillo-Ruiz","sequence":"additional","affiliation":[{"name":"Escuela de Qu\u00edmica y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago 8370149, Chile"},{"name":"Departamento de Ciencias Qu\u00edmicas y Biol\u00f3gicas, Facultad de Ciencias de la Salud, Universidad Bernardo O\u2019Higgins, Santiago 8370854, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Velarde","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Universidad de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdiel","family":"Salgado","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valpara\u00edso, Universidad de Valpara\u00edso, Pasaje Harrington 287, Playa Ancha, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3811-0347","authenticated-orcid":false,"given":"Juan C.","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valpara\u00edso, Universidad de Valpara\u00edso, Pasaje Harrington 287, Playa Ancha, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S0735-1097(03)00088-3","article-title":"Atherothrombosis, inflammation, and diabetes","volume":"41","author":"Abbate","year":"2003","journal-title":"J. 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