A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity

Balázs Csóka, Gábor Töro, Joana Vindeirinho, Zoltán V. Varga, Balázs Koscsó, Zoltán H. Németh, Endre Kókai, Luca Antonioli, Mara Suleiman, Piero Marchetti, Karolina Cseri, Ádám Deák, László Virág, Pál Pacher, Péter Bai, György Haskó

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Adenosine, a key extracellular signalingmediator, regulates several aspects of metabolismby activating 4 G-protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)-induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR-knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD. This impaired glucose tolerance was caused by a decrease in insulin secretion but not in insulin sensitivity. Islet size and insulin content in pancreata ofA2AAR-deficient micewere decreased comparedwith controlmice after consuming an HFD. A2AAR-KO mice had decreased expression of the β-cell-specific markers pdx1, glut2, mafA, and nkx6.1 and increased expression of the dedifferentiation markers sox2 and hes1. Ex vivo islet experiments confirmedthe role ofA2AARs in protecting against decreased insulin content and release caused by HFD. Other experiments with bone marrow chimeras revealed that inflammation was not the primary cause of decreased insulinsecretionin A2AAR-KOmice. Altogether,our data showedthatA2AARscontrol pancreatic dysfunction inHFDinduced obesity.

Original languageEnglish
Pages (from-to)4985-4997
Number of pages13
JournalFASEB Journal
Volume31
Issue number11
DOIs
Publication statusPublished - 2017

Keywords

  • Diabetes
  • Islet
  • β-cell
  • β-cell dedifferentiation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'A<sub>2A</sub> adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity'. Together they form a unique fingerprint.

  • Cite this

    Csóka, B., Töro, G., Vindeirinho, J., Varga, Z. V., Koscsó, B., Németh, Z. H., Kókai, E., Antonioli, L., Suleiman, M., Marchetti, P., Cseri, K., Deák, Á., Virág, L., Pacher, P., Bai, P., & Haskó, G. (2017). A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. FASEB Journal, 31(11), 4985-4997. https://doi.org/10.1096/fj.201700398R