{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:12:54Z","timestamp":1790719974573,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundations of China","award":["81500635"],"award-info":[{"award-number":["81500635"]}]},{"name":"the Department of Science and Technology of Jilin Province","award":["20190201151JC, 20200403043SF"],"award-info":[{"award-number":["20190201151JC, 20200403043SF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet \u03b2-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet \u03b2 cells in response to lipotoxicity.<\/jats:p>","DOI":"10.3390\/ijms21197161","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T10:39:58Z","timestamp":1601289598000},"page":"7161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["MKP-5 Relieves Lipotoxicity-Induced Islet \u03b2-Cell Dysfunction and Apoptosis via Regulation of Autophagy"],"prefix":"10.3390","volume":"21","author":[{"given":"Tongjian","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Teng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqun","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/osp4.112","article-title":"Cognitive effects of a 30-min aerobic exercise bout on adults with overweight\/obesity and type 2 diabetes","volume":"3","author":"Vincent","year":"2017","journal-title":"Obes. 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