A Guanidine-rich Regulatory Oligodeoxynucleotide Improves Type-2 Diabetes in Obese Mice by Blocking T-cell Differentiation

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A Guanidine-rich Regulatory Oligodeoxynucleotide Improves Type-2 Diabetes in Obese Mice by Blocking T-cell Differentiation

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Title: A Guanidine-rich Regulatory Oligodeoxynucleotide Improves Type-2 Diabetes in Obese Mice by Blocking T-cell Differentiation
Author: Cheng, Xiang; Wang, Jing; Xia, Ni; Yan, Xin-Xin; Tang, Ting-Ting; Chen, Han; Zhang, Hong-Jian; Liu, Juan; Kong, Wen; Sjöberg, Sara; Folco, Eduardo; Libby, Peter; Liao, Yu-Hua; Shi, Guo-Ping

Note: Order does not necessarily reflect citation order of authors.

Citation: Cheng, Xiang, Jing Wang, Ni Xia, Xin-Xin Yan, Ting-Ting Tang, Han Chen, Hong-Jian Zhang, et al. 2012. A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation. EMBO Molecular Medicine 4(10): 1112-1125.
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Abstract: T lymphocytes exhibit pro-inflammatory or anti-inflammatory activities in obesity and diabetes, depending on their subtypes. Guanidine-rich immunosuppressive oligodeoxynucleotides (ODNs) effectively control Th1/Th2-cell counterbalance. This study reveals a non-toxic regulatory ODN (ODNR01) that inhibits Th1- and Th17-cell polarization by binding to STAT1/3/4 and blocking their phosphorylation without affecting Th2 and regulatory T cells. ODNR01 improves glucose tolerance and insulin sensitivity in both diet-induced obese (DIO) and genetically generated obese (ob/ob) mice. Mechanistic studies show that ODNR01 suppresses Th1- and Th17-cell differentiation in white adipose tissue, thereby reducing macrophage accumulation and M1 macrophage inflammatory molecule expression without affecting M2 macrophages. While ODNR01 shows no effect on diabetes in lymphocyte-free Rag1-deficient DIO mice, it enhances glucose tolerance and insulin sensitivity in CD4\(^+\) T-cell-reconstituted Rag1-deficient DIO mice, suggesting its beneficial effect on insulin resistance is T-cell-dependent. Therefore, regulatory ODNR01 reduces obesity-associated insulin resistance through modulation of T-cell differentiation.
Published Version: doi:10.1002/emmm.201201272
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491840/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10589815
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