{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T20:53:48Z","timestamp":1769806428001,"version":"3.49.0"},"reference-count":100,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:p>Insulin resistance (IR) is a pathogenic mechanism for type 2 diabetes mellitus (T2DM), and receptor-interacting serine\u2013threonine kinase 2 (RIPK2) participates in mediating IR. To investigate the specific role of RIPK2 in IR, this study utilized bovine serum albumin-conjugated palmitic acid (0.5 mmol\/L) to create an IR model in rat L6 myotubes, followed by transfection with\/without short hairpin RNA against RIPK2 (shRIPK2)\/RIPK2 overexpression plasmid, and X-linked inhibitor of apoptosis (XIAP) overexpression plasmids. The expressions of RIPK2 and XIAP were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress markers superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were quantified. Western blot was performed to detect the levels of phosphorylation of extracellular signal-regulated kinases 1\/2 (p-ERK1\/2)\/ERK1\/2, p-p38\/p38, and p-serine\/threonine kinase (p-AKT)\/AKT, as well as the influence of XIAP on RIPK2 ubiquitination. Glucose absorption was quantified using fluorescent probes (2-NBDG). In the IR model, RIPK2 expression was significantly increased, whereas XIAP expression was reduced. RIPK2 overexpression diminished SOD levels, CAT levels, and GPx levels and elevated MDA levels, accompanied by increased p-ERK1\/2\/ERK1\/2 and p-p38\/p38 ratios. Overexpression of RIPK2 lowered glucose absorption and the p-AKT\/AKT ratio. RIPK2 was ubiquitinated by XIAP in the IR model. RIPK2 overexpression offset the impact of XIAP overexpression on SOD levels, CAT levels, GPx levels, and MDA levels, p-ERK1\/2\/ERK1\/2 ratios, and p-p38\/p38 ratios. XIAP overexpression enhanced glucose absorption and the p-AKT\/AKT ratio. Our results demonstrate that XIAP deficiency reduces RIPK2 ubiquitination, thereby mediating IR in T2DM.<\/jats:p>","DOI":"10.1530\/ec-25-0429","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T10:46:16Z","timestamp":1765881976000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["XIAP down-regulation inhibits RIPK2 ubiquitination-mediated insulin resistance"],"prefix":"10.1530","volume":"15","author":[{"given":"Chunnan","family":"Zhao","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Chengde Medical University Clinical Laboratory, Chengde, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zezhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Chengde Medical University Clinical Laboratory, Chengde, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Chengde Medical University Clinical Laboratory, Chengde, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1371-6717","authenticated-orcid":true,"given":"Xueli","family":"Geng","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Chengde Medical University Clinical Laboratory, Chengde, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"416","reference":[{"key":"bib1","series-title":"WMJ","first-page":"167","article-title":"Diabetes mellitus-not just type 1 or type 2 anymore","volume":"117","author":"Riaz A","year":"2018","unstructured":"Riaz A\n & \nDolan MJ\n\n. 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