{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:27:09Z","timestamp":1770751629625,"version":"3.50.0"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF0710503"],"award-info":[{"award-number":["2022YFF0710503"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cultivation Project of the Science and Technology Platform by the Education Department of Liaoning Province","award":["LJ232410161039"],"award-info":[{"award-number":["LJ232410161039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, progressive \u03b2-cell dysfunction, and insulin resistance. While numerous chemically induced and transgenic rodent models exist, spontaneous models recapitulating natural type 2 diabetes mellitus (T2DM) progression remain scarce. Here, we characterize Myodes rufocanus as a novel spontaneous T2DM model through comprehensive assessments of 18-week-old male F6 voles, demonstrating hallmark diabetic features including weight gain, hyperphagia, polydipsia, hyperglycemia, insulin resistance, and dyslipidemia. Pancreatic transcriptomic profiling revealed pronounced COX14 (cytochrome c oxidase assembly factor 14) downregulation, as validated by qPCR and Western blotting in pancreatic tissue and MIN6 \u03b2-cells. MIN6 cells under chronic high-glucose conditions (30 mM) exhibited diminished mitochondrial membrane potential, impaired ATP biosynthesis, elevated reactive oxygen species, and attenuated glucose-stimulated insulin secretion, with consistent COX14 downregulation suggesting potential association with mitochondrial dysfunction. Additionally, suppressed Nrf2\u2013HO-1 antioxidant signaling appeared to compound cellular injury, with intrinsic apoptotic pathway activation indicated by elevated Bax\/Bcl-2 ratios and caspase-3 activity. These findings establish M. rufocanus as a valuable spontaneous T2DM model and implicate COX14 downregulation as a potential correlate of mitochondrial impairment and \u03b2-cell failure in diabetes pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms27031539","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:55:11Z","timestamp":1770216911000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics Analysis of a Spontaneous Type 2 Diabetes Model in Myodes rufocanus and Its Underlying Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4192-6034","authenticated-orcid":false,"given":"Ijaz","family":"Ullah","sequence":"first","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haseena","family":"Mujeeb","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qindan","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingxuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habib","family":"Alam","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section, South Lvshun Road, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0615-8868","authenticated-orcid":false,"given":"Mujeeb Ur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiazheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanpin","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-8276","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Comparative Medicine Department of Research and Teaching, Dalian Medical University, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Dalian Medical University Dalian, Dalian 116044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s42255-024-01190-w","article-title":"Diabetes in China: Epidemiology, pathophysiology and multi-omics","volume":"7","author":"Jia","year":"2025","journal-title":"Nat. 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