PuSH - Publikationsserver des Helmholtz Zentrums München

Lorza-Gil, E. ; Kaiser, G. ; Rexen Ulven, E.* ; König, G.M.* ; Gerst, F. ; Oquendo, M.B.* ; Birkenfeld, A.L. ; Häring, H.-U. ; Kostenis, E.* ; Ulven, T.* ; Ullrich, S.

FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: A comparative study with mouse islets and rat INS-1E cells.

Sci. Rep. 10:16497 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The expression of short chain fatty acid receptors FFA2 and FFA3 in pancreatic islets raised interest in using them as drug targets for treating hyperglycemia in humans. This study aims to examine the efficacy of synthetic FFA2- and FFA3-ligands to modulate glucose-stimulated insulin secretion (GSIS) in human pseudoislets which display intact glucose responsiveness. The FFA2-agonists 4-CMTB and TUG-1375 inhibited GSIS, an effect reversed by the FFA2-antagonist CATPB. GSIS itself was not augmented by CATPB. The FFA3-agonists FHQC and 1-MCPC did not affect GSIS in human pseudoislets. For further drug evaluation we used mouse islets. The CATPB-sensitive inhibitory effect of 100 mu M 4-CMTB on GSIS was recapitulated. The inhibition was partially sensitive to the G(i/o)-protein inhibitor pertussis toxin. A previously described FFA2-dependent increase of GSIS was observed with lower concentrations of 4-CMTB (10 and 30 mu M). The stimulatory effect of 4-CMTB on secretion was prevented by the Gq-protein inhibitor FR900359. As in human pseudoislets, in mouse islets relative mRNA levels were FFAR2 > FFAR3 and FFA3-agonists did not affect GSIS. The FFA3-agonists, however, inhibited GSIS in a pertussis toxin-sensitive manner in INS-1E cells and this correlated with relative mRNA levels of Ffar3 > > Ffar2. Thus, in humans, when FFA2-activation impedes GSIS, FFA2-antagonism may reduce glycemia.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chain Fatty-acids; Pancreatic Beta-cells; Insulin-secretion; Functional-characterization; Gene-expression; Pyy Secretion; Receptor 2; Protein; Gpr43; Agonists
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 16497 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Projekt DEAL