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

Balázs Csóka, Gábor Törő, Joana Vindeirinho, Zoltán V. Varga, Balázs Koscsó, Zoltán H. Németh, Endre Kókai, Luca Antonioli, Mara Suleiman, Piero Marchetti, Karolina Cseri, Ádám Deák, L. Virág, Pál Pacher, P. Bai, G. Haskó

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by 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 of A2AAR-deficient mice were decreased compared with control mice 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 confirmed the role of A2AARs 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 insulin secretion in A2AAR-KO mice. Altogether, our data showed that A2AARs control pancreatic dysfunction in HFD-induced obesity.-Csóka, B., Törő, 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. A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity.

Original languageEnglish
Pages (from-to)4985-4997
Number of pages13
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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Adenosine A2A Receptors
High Fat Diet
Nutrition
Obesity
Fats
Insulin
Knockout Mice
Glucose Intolerance
Glucose
Adenosine A2B Receptors
Adenosine A3 Receptors
Adenosine A1 Receptors
Metabolism
Adenosine
Insulin Resistance
Pancreas
Bone
Homeostasis
Bone Marrow
Experiments

Keywords

  • diabetes
  • islet
  • β-cell
  • β-cell dedifferentiation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. / Csóka, Balázs; Törő, Gábor; Vindeirinho, Joana; Varga, Zoltán V.; Koscsó, Balázs; Németh, Zoltán H.; Kókai, Endre; Antonioli, Luca; Suleiman, Mara; Marchetti, Piero; Cseri, Karolina; Deák, Ádám; Virág, L.; Pacher, Pál; Bai, P.; Haskó, G.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 31, No. 11, 01.11.2017, p. 4985-4997.

Research output: Contribution to journalArticle

Csóka, B, Törő, G, Vindeirinho, J, Varga, ZV, Koscsó, B, Németh, ZH, 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 : official publication of the Federation of American Societies for Experimental Biology, vol. 31, no. 11, pp. 4985-4997. https://doi.org/10.1096/fj.201700398R
Csóka, Balázs ; Törő, Gábor ; Vindeirinho, Joana ; Varga, Zoltán V. ; Koscsó, Balázs ; Németh, Zoltán H. ; Kókai, Endre ; Antonioli, Luca ; Suleiman, Mara ; Marchetti, Piero ; Cseri, Karolina ; Deák, Ádám ; Virág, L. ; Pacher, Pál ; Bai, P. ; Haskó, G. / A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2017 ; Vol. 31, No. 11. pp. 4985-4997.
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