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Increased number of islet-associated macrophages in type 2 diabetes

Ehses, J A; Perren, A; Eppler, E; Ribaux, P; Pospisilik, J A; Maor-Cahn, R; Gueripel, X; Ellingsgaard, H; Schneider, M K J; Biollaz, G; Fontana, A; Reinecke, M; Homo-Delarche, F; Donath, M Y (2007). Increased number of islet-associated macrophages in type 2 diabetes. Diabetes, 56(9):2356-2370.

Abstract

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat-fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat-fed mice, increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC, granulocyte colony-stimulating factor, and macrophage inflammatory protein 1alpha. The specificity of this response was investigated by direct comparison to nonislet pancreatic tissue and beta-cell lines and was not mimicked by the induction of islet cell death. Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8 neutralization, and IL-8 was localized to the human pancreatic alpha-cell. Therefore, islet-derived inflammatory factors are regulated by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type 2 diabetes.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Internal Medicine
Health Sciences > Endocrinology, Diabetes and Metabolism
Language:English
Date:September 2007
Deposited On:19 Mar 2009 13:41
Last Modified:02 May 2025 01:38
Publisher:American Diabetes Association
ISSN:0012-1797
Additional Information:This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes (http://diabetes.diabetesjournals.org). The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available online at [DOI of the online article].
OA Status:Hybrid
Publisher DOI:https://doi.org/10.2337/db06-1650
PubMed ID:17579207

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