Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7171965 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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MG53 Does Not Manifest the Development of Diabetes in <i>db/db</i> Mice.

Wang Qiang Q Bian Zehua Z Jiang Qiwei Q Wang Xiaoliang X Zhou Xinyu X Park Ki Ho KH Hsueh Willa W Whitson Bryan A BA Haggard Erin E Li Haichang H Chen Ken K Cai Chuanxi C Tan Tao T Zhu Hua H Ma Jianjie J

Diabetes 20200305 5

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 <i>db/db</i> 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 antibo ...[more]

PMID: 32139593

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Project description:IntroductionThe rapid expansion of Type 2 Diabetes (T2D), that currently affects 90% of people suffering from diabetes, urges us to develop a better understanding of the metabolic processes involved in the disease process in order to develop better therapies. The most commonly used model for T2D research is the db/db (BKS.Cg-Dock7 < m > +/+ Lepr < db >/J) mouse model. Yet, a systematic 1H NMR based metabolomics characterisation of most tissues in this animal model has not been published. Here, we provide a systematic organ-specific metabolomics analysis of this widely employed model using NMR spectroscopy.ObjectivesThe aim of this study was to characterise the metabolic modulations associated with T2D in db/db mice in 18 relevant biological matrices.MethodsHigh-resolution 1H-NMR and 2D-NMR spectroscopy were applied to 18 biological matrices of 12 db/db mice (WT control n = 6, db/db = 6) aged 22 weeks, when diabetes is fully established.Results61 metabolites associated with T2D were identified. Kidney, spleen, eye and plasma were the biological matrices carrying the largest metabolomics modulations observed in established T2D, based on the total number of metabolites that showed a statistical difference between the diabetic and control group in each tissue (16 in each case) and the strength of the O-PLS DA model for each tissue. Glucose and glutamate were the most commonly associated metabolites found significantly increased in nine biological matrices. Investigated sections where no increase of glucose was associated with T2D include all intestinal segments (i.e. duodenum, jejunum, ileum and colon). Microbial co-metabolites such as acetate and butyrate, used as carbon sources by the host, were identified in excess in the colonic tissues of diabetic individuals.ConclusionsThe metabolic biomarkers identified using 1H NMR-based metabolomics will represent a useful resource to explore metabolic pathways involved in T2D in the db/db mouse model.

Dataset Information

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

Publications

MG53 Does Not Manifest the Development of Diabetes in <i>db/db</i> Mice.

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