{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T15:36:25Z","timestamp":1775576185219,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordinaci\u00f3n de Posgrado e Investigaci\u00f3n\u2010UABC","award":["Grant no. 106\/2\/N\/57\/1; 1983"],"award-info":[{"award-number":["Grant no. 106\/2\/N\/57\/1; 1983"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic overload by saturated fatty acids (SFA), which comprises \u03b2-cell function, and impaired glucose-stimulated insulin secretion are frequently observed in patients suffering from obesity and type 2 diabetes mellitus. The increase of intracellular Ca2+ triggers insulin granule release, therefore several mechanisms regulate Ca2+ efflux within the \u03b2-cells, among others, the plasma membrane Ca2+-ATPase (PMCA). In this work, we describe that lipotoxicity mediated mainly by the saturated palmitic acid (PA) (16C) is associated with loss of protein homeostasis (proteostasis) and potentially cell viability, a phenomenon that was induced to a lesser extent by stearic (18C), myristic (14C) and lauric (12C) acids. PA was localized on endoplasmic reticulum, activating arms of the unfolded protein response (UPR), as also promoted by lipopolysaccharides (LPS)-endotoxins. In particular, our findings demonstrate an alteration in PMCA1\/4 expression caused by PA and LPS which trigger the UPR, affecting not only insulin release and contributing to \u03b2-cell mass reduction, but also increasing reactive nitrogen species. Nonetheless, stearic acid (SA) did not show these effects. Remarkably, the proteolytic degradation of PMCA1\/4 prompted by PA and LPS was avoided by the action of monounsaturated fatty acids such as oleic and palmitoleic acid. Oleic acid recovered cell viability after treatment with PA\/LPS and, more interestingly, relieved endoplasmic reticulum (ER) stress. While palmitoleic acid improved the insulin release, this fatty acid seems to have more relevant effects upon the expression of regulatory pumps of intracellular Ca2+. Therefore, chain length and unsaturation of fatty acids are determinant cues in proteostasis of \u03b2-cells and, consequently, on the regulation of calcium and insulin secretion.<\/jats:p>","DOI":"10.3390\/cells8080884","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T03:59:26Z","timestamp":1565755166000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Fatty Acid and Lipopolysaccharide Effect on Beta Cells Proteostasis and its Impact on Insulin Secretion"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5075-2863","authenticated-orcid":false,"given":"Paloma","family":"Acosta-Monta\u00f1o","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, 21000 Mexicali, Mexico"}]},{"given":"Eustolia","family":"Rodr\u00edguez-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Facultad de Odontolog\u00eda, Universidad Aut\u00f3noma de Baja California, 22390 Tijuana, Mexico"},{"name":"Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Tijuana, Centro de Graduados e Investigaci\u00f3n en Qu\u00edmica-Grupo de Biomateriales y Nanomedicina, 22510 Tijuana, Mexico"}]},{"given":"Esmeralda","family":"Ibarra-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, 21000 Mexicali, Mexico"}]},{"given":"H\u00e9ctor","family":"Frayde-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, 21000 Mexicali, Mexico"},{"name":"Hospital General de Zona No. 30, Instituto Mexicano del Seguro Social, 21100 Mexicali, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-6993","authenticated-orcid":false,"given":"Jaime","family":"Mas-Oliva","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, 04510 Ciudad de M\u00e9xico, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6822-3302","authenticated-orcid":false,"given":"Blanca","family":"Delgado-Coello","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, 04510 Ciudad de M\u00e9xico, Mexico"}]},{"given":"Ignacio A.","family":"Rivero","sequence":"additional","affiliation":[{"name":"Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Tijuana, Centro de Graduados e Investigaci\u00f3n en Qu\u00edmica, 22000 Tijuana, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3301-9619","authenticated-orcid":false,"given":"Manuel","family":"Alatorre-Meda","sequence":"additional","affiliation":[{"name":"C\u00e1tedras CONACyT- Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Tijuana. Centro de Graduados e Investigaci\u00f3n en Qu\u00edmica-Grupo de Biomateriales y Nanomedicina, 22000 Tijuana, Mexico"}]},{"given":"Jorge","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Tijuana, Centro de Graduados e Investigaci\u00f3n en Qu\u00edmica, 22000 Tijuana, Mexico"}]},{"given":"Lizbeth","family":"Guevara-Olaya","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, 21000 Mexicali, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-3730","authenticated-orcid":false,"given":"Victor","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, 21000 Mexicali, Mexico"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/dom.12727","article-title":"Pancreatic beta-cell identity in diabetes","volume":"18","author":"Remedi","year":"2016","journal-title":"Diabetes Obes. 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