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MG53 Does Not Manifest the Development of Diabetes in db/db Mice

MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53’s role in insulin signaling and manifestation of diabetes. We generated db/db mice with either whole-body ablation or sustained...

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Autores principales: Wang, Qiang, Bian, Zehua, Jiang, Qiwei, Wang, Xiaoliang, Zhou, Xinyu, Park, Ki Ho, Hsueh, Willa, Whitson, Bryan A., Haggard, Erin, Li, Haichang, Chen, Ken, Cai, Chuanxi, Tan, Tao, Zhu, Hua, Ma, Jianjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171965/
https://www.ncbi.nlm.nih.gov/pubmed/32139593
http://dx.doi.org/10.2337/db19-0807
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author Wang, Qiang
Bian, Zehua
Jiang, Qiwei
Wang, Xiaoliang
Zhou, Xinyu
Park, Ki Ho
Hsueh, Willa
Whitson, Bryan A.
Haggard, Erin
Li, Haichang
Chen, Ken
Cai, Chuanxi
Tan, Tao
Zhu, Hua
Ma, Jianjie
author_facet Wang, Qiang
Bian, Zehua
Jiang, Qiwei
Wang, Xiaoliang
Zhou, Xinyu
Park, Ki Ho
Hsueh, Willa
Whitson, Bryan A.
Haggard, Erin
Li, Haichang
Chen, Ken
Cai, Chuanxi
Tan, Tao
Zhu, Hua
Ma, Jianjie
author_sort Wang, Qiang
collection PubMed
description MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53’s 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.
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spelling pubmed-71719652020-05-06 MG53 Does Not Manifest the Development of Diabetes in db/db Mice Wang, Qiang Bian, Zehua Jiang, Qiwei Wang, Xiaoliang Zhou, Xinyu Park, Ki Ho Hsueh, Willa Whitson, Bryan A. Haggard, Erin Li, Haichang Chen, Ken Cai, Chuanxi Tan, Tao Zhu, Hua Ma, Jianjie Diabetes Pharmacology and Therapeutics MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53’s 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. American Diabetes Association 2020-05 2020-03-05 /pmc/articles/PMC7171965/ /pubmed/32139593 http://dx.doi.org/10.2337/db19-0807 Text en © 2020 by the American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Pharmacology and Therapeutics
Wang, Qiang
Bian, Zehua
Jiang, Qiwei
Wang, Xiaoliang
Zhou, Xinyu
Park, Ki Ho
Hsueh, Willa
Whitson, Bryan A.
Haggard, Erin
Li, Haichang
Chen, Ken
Cai, Chuanxi
Tan, Tao
Zhu, Hua
Ma, Jianjie
MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title_full MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title_fullStr MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title_full_unstemmed MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title_short MG53 Does Not Manifest the Development of Diabetes in db/db Mice
title_sort mg53 does not manifest the development of diabetes in db/db mice
topic Pharmacology and Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171965/
https://www.ncbi.nlm.nih.gov/pubmed/32139593
http://dx.doi.org/10.2337/db19-0807
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