Imperial College London
Alternate

ProfessorMarinaBotto

Faculty of Medicine, Department of Immunology and Inflammation

Head of Department, Director of Bioservices
 
 
 
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Contact

 

+44 (0)20 3313 2316m.botto Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N10Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tanigaki:2017:10.1172/JCI89333,
author = {Tanigaki, K and Sacharidou, A and Peng, J and Chambliss, KL and Yuhanna, IS and Ghosh, D and Ahmed, M and Szalai, AJ and Vongpatanasin, W and Mattrey, RF and Chen, Q and Azadi, P and Lingvay, I and Botto, M and Holland, WL and Kohler, JJ and Sirsi, SR and Hoyt, K and Shaul, PW and Mineo, C},
doi = {10.1172/JCI89333},
journal = {Journal of Clinical Investigation},
pages = {309--322},
title = {Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance.},
url = {http://dx.doi.org/10.1172/JCI89333},
volume = {128},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Type 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we have shown that activation of the IgG receptor FcγRIIB in endothelium by hyposialylated IgG plays an important role in obesity-induced insulin resistance. Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or selectively in endothelium were protected from insulin resistance as a result of the preservation of insulin delivery to skeletal muscle and resulting maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin resistance. Moreover, IgG transferred from patients with T2DM but not from metabolically healthy subjects caused insulin resistance in IgG-deficient mice via FcγRIIB, indicating that similar processes may be operative in T2DM in humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice impaired endothelial cell insulin transcytosis in culture and in vivo. These effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. Thus, IgG sialylation and endothelial FcγRIIB may represent promising therapeutic targets to sever the link between obesity and T2DM.
AU  - Tanigaki,K
AU  - Sacharidou,A
AU  - Peng,J
AU  - Chambliss,KL
AU  - Yuhanna,IS
AU  - Ghosh,D
AU  - Ahmed,M
AU  - Szalai,AJ
AU  - Vongpatanasin,W
AU  - Mattrey,RF
AU  - Chen,Q
AU  - Azadi,P
AU  - Lingvay,I
AU  - Botto,M
AU  - Holland,WL
AU  - Kohler,JJ
AU  - Sirsi,SR
AU  - Hoyt,K
AU  - Shaul,PW
AU  - Mineo,C
DO  - 10.1172/JCI89333
EP  - 322
PY  - 2017///
SN  - 0021-9738
SP  - 309
TI  - Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance.
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI89333
UR  - http://hdl.handle.net/10044/1/54592
VL  - 128
ER  -
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