{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:52:16Z","timestamp":1788864736577,"version":"build-2803163510"},"reference-count":49,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970260"],"award-info":[{"award-number":["81970260"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2022NSFSC0671"],"award-info":[{"award-number":["2022NSFSC0671"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:p>MG53 is predominantly expressed in striated muscles. The role of MG53 in diabetes has gradually been elucidated but is still full of controversy. Some reports have indicated that MG53 is upregulated in animal models with metabolic disorders and that muscle-specific MG53 upregulation is sufficient to induce whole-body insulin resistance and metabolic syndrome through targeting both the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) for ubiquitin-dependent degradation. Additionally, MG53 has been identified as a myokine\/cardiokine that is secreted from striated muscles into the bloodstream, and circulating MG53 has further been shown to trigger insulin resistance by binding to the extracellular domain of the IR, thereby allosterically inhibiting insulin signaling. Conversely, findings have been reported from other studies that contradict these results. Specifically, no significant change in MG53 expression in striated muscles or serum has been observed in diabetic models, and the MG53-mediated degradation of IRS-1 may be insufficient to induce insulin resistance due to the compensatory roles of other IRS subtypes. Furthermore, sustained elevation of MG53 levels in serum or systemic administration of recombinant human MG53 (rhMG53) has shown no impact on metabolic function. In this article, we will fully characterize these two disparate views, strive to provide critical insights into their contrasts, and propose several specific experimental approaches that may yield additional evidence. Our goal is to encourage the scientific community to elucidate the effects of MG53 on metabolic diseases and the molecular mechanisms involved, thereby providing the theoretical basis for the treatment of metabolic diseases and the applications of rhMG53.<\/jats:p>","DOI":"10.2337\/db24-0556","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T16:34:31Z","timestamp":1731515671000},"page":"145-152","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":6,"title":["Friend or Foe: The Paradoxical Roles of MG53 in Diabetes"],"prefix":"10.2337","volume":"74","author":[{"given":"Shuangshuang","family":"Yuan","sequence":"first","affiliation":[{"name":"1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, and Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yu","sequence":"additional","affiliation":[{"name":"1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, and Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Luo","sequence":"additional","affiliation":[{"name":"1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, and Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Wu","sequence":"additional","affiliation":[{"name":"1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, and Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China"},{"name":"2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3362-0444","authenticated-orcid":false,"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[{"name":"1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, and Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China"},{"name":"2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"2025012119510232600_B1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1056\/NEJM199001253220403","article-title":"Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy","volume":"322","author":"Shulman","year":"1990","journal-title":"N Engl J Med"},{"key":"2025012119510232600_B2","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1056\/NEJM199312303292703","article-title":"Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. 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