Increased number of islet-associated macrophages in type 2 diabetes.
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.
Ehses
Jan A
JA
Division of Endocrinology and Diabetes and Center for Integrated Human Physiology, University Hospital of Zürich, Zürich, Switzerland. jan.ehses@usz.ch
Perren
Aurel
A
Eppler
Elisabeth
E
Ribaux
Pascale
P
Pospisilik
John A
JA
Maor-Cahn
Ranit
R
Gueripel
Xavier
X
Ellingsgaard
Helga
H
Schneider
Marten K J
MK
Biollaz
Gregoire
G
Fontana
Adriano
A
Reinecke
Manfred
M
Homo-Delarche
Francoise
F
Donath
Marc Y
MY
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
D015703:Antigens, CD; D015235:HLA-B Antigens