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Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes

Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and...

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Autores principales: Dharmadhikari, Gitanjali, Stolz, Katharina, Hauke, Michael, Morgan, Noel G., Varki, Ajit, de Koning, Eelco, Kelm, Sørge, Maedler, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381285/
https://www.ncbi.nlm.nih.gov/pubmed/28378743
http://dx.doi.org/10.1038/srep45319
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author Dharmadhikari, Gitanjali
Stolz, Katharina
Hauke, Michael
Morgan, Noel G.
Varki, Ajit
de Koning, Eelco
Kelm, Sørge
Maedler, Kathrin
author_facet Dharmadhikari, Gitanjali
Stolz, Katharina
Hauke, Michael
Morgan, Noel G.
Varki, Ajit
de Koning, Eelco
Kelm, Sørge
Maedler, Kathrin
author_sort Dharmadhikari, Gitanjali
collection PubMed
description Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival.
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spelling pubmed-53812852017-04-10 Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes Dharmadhikari, Gitanjali Stolz, Katharina Hauke, Michael Morgan, Noel G. Varki, Ajit de Koning, Eelco Kelm, Sørge Maedler, Kathrin Sci Rep Article Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival. Nature Publishing Group 2017-04-05 /pmc/articles/PMC5381285/ /pubmed/28378743 http://dx.doi.org/10.1038/srep45319 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Dharmadhikari, Gitanjali
Stolz, Katharina
Hauke, Michael
Morgan, Noel G.
Varki, Ajit
de Koning, Eelco
Kelm, Sørge
Maedler, Kathrin
Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title_full Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title_fullStr Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title_full_unstemmed Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title_short Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
title_sort siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381285/
https://www.ncbi.nlm.nih.gov/pubmed/28378743
http://dx.doi.org/10.1038/srep45319
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