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Controversy exists regarding MG53\u2019s role in insulin signaling and manifestation of diabetes. We generated db\/db mice with either whole-body ablation or sustained elevation of MG53 in the bloodstream in order to evaluate the physiological function of MG53 in diabetes. To quantify the amount of MG53 protein in circulation, we developed a monoclonal antibody against MG53 with high specificity. Western blot using this antibody revealed lower or no change of serum MG53 levels in db\/db mice or patients with diabetes compared with control subjects. Neither whole-body ablation of MG53 nor sustained elevation of MG53 in circulation altered insulin signaling and glucose handling in db\/db mice. Instead, mice with ablation of MG53 were more susceptible to streptozotocin-induced dysfunctional handling of glucose compared with the wild-type littermates. Alkaline-induced corneal injury demonstrated delayed healing in db\/db mice, which was restored by topical administration of recombinant human (rh)MG53. Daily intravenous administration of rhMG53 in rats at concentrations up to 10 mg\/kg did not produce adverse effects on glucose handling. These findings challenge the hypothetical function of MG53 as a causative factor for the development of diabetes. Our data suggest that rhMG53 is a potentially safe and effective biologic to treat diabetic oculopathy in rodents.<\/jats:p>","DOI":"10.2337\/db19-0807","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T03:45:15Z","timestamp":1583466315000},"page":"1052-1064","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":49,"title":["MG53 Does Not Manifest the Development of Diabetes in <i>db\/db<\/i> Mice"],"prefix":"10.2337","volume":"69","author":[{"given":"Qiang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehua","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, 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