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Citations to this article

Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance
Keiji Tanigaki, … , Philip W. Shaul, Chieko Mineo
Keiji Tanigaki, … , Philip W. Shaul, Chieko Mineo
Published November 27, 2017
Citation Information: J Clin Invest. 2018;128(1):309-322. https://doi.org/10.1172/JCI89333.
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Research Article Metabolism Vascular biology Article has an altmetric score of 56

Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance

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Abstract

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.

Authors

Keiji Tanigaki, Anastasia Sacharidou, Jun Peng, Ken L. Chambliss, Ivan S. Yuhanna, Debabrata Ghosh, Mohamed Ahmed, Alexander J. Szalai, Wanpen Vongpatanasin, Robert F. Mattrey, Qiushi Chen, Parastoo Azadi, Ildiko Lingvay, Marina Botto, William L. Holland, Jennifer J. Kohler, Shashank R. Sirsi, Kenneth Hoyt, Philip W. Shaul, Chieko Mineo

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 Total
Citations: 4 7 12 6 13 7 9 2 60
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2019 (9)

Title and authors Publication Year
SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis
L Huang, KL Chambliss, X Gao, IS Yuhanna, E Behling-Kelly, S Bergaya, M Ahmed, P Michaely, K Luby-Phelps, A Darehshouri, L Xu, EA Fisher, WP Ge, C Mineo, PW Shaul
Nature 2019
Glycosylation in health and disease
C Reily, TJ Stewart, MB Renfrow, J Novak
Nature Reviews Nephrology 2019
Serum Amyloid P and a Dendritic Cell–Specific Intercellular Adhesion Molecule-3–Grabbing Nonintegrin Ligand Inhibit High-Fat Diet–Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice
D Pilling, N Cox, MA Thomson, TR Karhadkar, RH Gomer
The American Journal of Pathology 2019
Type 2 Diabetes: How Much of an Autoimmune Disease?
P de Candia, F Prattichizzo, S Garavelli, VD Rosa, M Galgani, FD Rella, MI Spagnuolo, A Colamatteo, C Fusco, T Micillo, S Bruzzaniti, A Ceriello, AA Puca, G Matarese
Frontiers in Endocrinology 2019
Supplementation with the Sialic Acid Precursor N-acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension
J Peng, W Vongpatanasin, A Sacharidou, D Kifer, IS Yuhanna, S Banerjee, K Tanigaki, O Polasek, H Chu, NC Sundgren, A Rohatgi, KL Chambliss, G Lauc, C Mineo, PW Shaul
Circulation 2019
Sialic acid metabolism as a potential therapeutic target of atherosclerosis
C Zhang, J Chen, Y Liu, D Xu
Lipids in Health and Disease 2019
An Inflammatory Story: Antibodies in Tuberculosis Comorbidities
MR McLean, LL Lu, SJ Kent, AW Chung
Frontiers in immunology 2019
Super-Resolution Ultrasound Imaging of Skeletal Muscle Microvascular Dysfunction in an Animal Model of Type 2 Diabetes: Super-Resolution Ultrasound Imaging of Microvascular Dysfunction
D Ghosh, J Peng, K Brown, S Sirsi, C Mineo, PW Shaul, K Hoyt
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 2019
Contrast-enhanced ultrasound imaging of acute changes in pancreatic cancer following targeted hyaluronan treatment
Oezdemir I, Javed K, Rijal G, Hoyt K
IEEE International Ultrasonics Symposium : [proceedings]. IEEE International Ultrasonics Symposium 2019

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