title: Increased number of islet-associated macrophages in type 2 diabetes.
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.
authors.affiliation: Division of Endocrinology and Diabetes and Center for Integrated Human Physiology, University Hospital of Zürich, Zürich, Switzerland. jan.ehses@usz.ch
authors.forename: Jan A
authors.initials: JA
authors.lastname: Ehses
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppler
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaux
authors.forename: John A
authors.initials: JA
authors.lastname: Pospisilik
authors.forename: Ranit
authors.initials: R
authors.lastname: Maor-Cahn
authors.forename: Xavier
authors.initials: X
authors.lastname: Gueripel
authors.forename: Helga
authors.initials: H
authors.lastname: Ellingsgaard
authors.forename: Marten K J
authors.initials: MK
authors.lastname: Schneider
authors.forename: Gregoire
authors.initials: G
authors.lastname: Biollaz
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinecke
authors.forename: Francoise
authors.initials: F
authors.lastname: Homo-Delarche
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D015235:HLA-B Antigens / Q000032:analysis; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology / Q000601:surgery
chemical_list: D015703:Antigens, CD; D015235:HLA-B Antigens