Skip to main content
main-content

04.03.2019 | Short Communication | Ausgabe 6/2019

Diabetologia 6/2019

Macrophage alterations in islets of obese mice linked to beta cell disruption in diabetes

Zeitschrift:
Diabetologia > Ausgabe 6/2019
Autoren:
Jeng Yie Chan, Kailun Lee, Emma L. Maxwell, Cassandra Liang, D. Ross Laybutt
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00125-019-4844-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Aims/hypothesis

Mild islet inflammation has been suggested as a contributing factor to beta cell failure in type 2 diabetes. Macrophage levels are elevated in the islets of humans and mice with type 2 diabetes, but their effects on beta cells are not understood. Our goal was to examine the gene expression changes in islet-associated macrophages in obesity models with opposing disposition to diabetes development and to assess their potential contribution to beta cell (mal)adaptation.

Methods

Islets were isolated from lean control mice, obese diabetes-prone db/db mice and obese diabetes-resistant ob/ob mice. Macrophages were sorted using flow cytometry. Islets were treated ex vivo with clodronate-containing liposomes to deplete macrophages. Gene expression was assessed by real-time RT-PCR.

Results

Macrophage levels were increased in islets from db/db mice but not in islets from ob/ob mice compared with lean control mice. Macrophages from db/db and ob/ob islets displayed distinct changes in gene expression compared with control islet macrophages, suggesting differential shifts in functional state. Macrophages from db/db islets displayed increased expression of interferon regulatory factor 5 (Irf5), IL-1 receptor antagonist (Il1rn) and mannose receptor C-type 1 (Mrc1), whereas macrophages from ob/ob islets showed elevated levels of transforming growth factor beta 1 (Tgfb1) and reduced IL-1β (Il1b). Clodronate-liposome treatment of islets depleted macrophages, as evidenced by reduced mRNA expression of Cd11b (also known as Itgam) and F4/80 (also known as Adgre1) compared with PBS-liposome-treated islets. The depletion of macrophages in db/db islets increased the expression of genes related to beta cell identity. The mRNA levels of islet-associated transcription factors (Mafa and Pdx1), glucose transporter (Glut2 [also known as Slc2a2]), ATP-sensitive K+ channel (Kcnj11), incretin receptor (Gipr) and adaptive unfolded protein response (UPR) genes (Xbp1, Hspa5, Pdia4 and Fkbp11) were increased in db/db islets after macrophage depletion, whereas the mRNA levels of the deleterious UPR effector, Ddit3, were reduced. In contrast, depletion of macrophages in islets of ob/ob mice did not affect beta cell identity gene expression.

Conclusions/interpretation

The findings of this study suggest that distinct alterations in islet macrophages of obese mice are critically important for the disruption of beta cell gene expression in diabetes.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt e.Med zum Sonderpreis bestellen!

Sichern Sie sich jetzt Ihr e.Med-Abo und sparen Sie 50 %!

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 6/2019

Diabetologia 6/2019 Zur Ausgabe
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Sie können e.Med Allgemeinmedizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.