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Lutz, S.Z. ; Ullrich, A.* ; Häring, H.-U. ; Ullrich, S. ; Gerst, F.

Sunitinib specifically augments glucose-induced insulin secretion.

Cell. Signal. 36, 91-97 (2017)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels and improves glycaemic control. This study aims to analyse whether sunitinib has specific and direct effects on insulin secreting β-cells. Regulation of insulin secretion, of cellular cAMP levels and activation of signalling pathways were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under specific stimulatory and inhibitory conditions. Secreted insulin and cellular cAMP levels were measured using RIA and ELISA, respectively. Protein phosphorylations were examined on western blots. Sunitinib enhanced glucose-induced insulin secretion (GIIS) concentration-dependently, reaching a maximal stimulation at 2μM. Sunitinib further augmented insulin secretion in the presence of elevated cAMP levels and the FFAR1 agonists. Adrenaline and the PKA inhibitor H89 counteracted the stimulatory effect of sunitinib on secretion. However, sunitinib altered neither the cellular levels of cAMP nor the phosphorylation of PKA. Sunitinib did not reduce IGF-1-induced phosphorylation of AKT/PKB and ERK1/2. In conclusion, these results suggest that sunitinib stimulates GIIS by a direct effect on β-cells, which may contribute to the glucose-lowering action of the tyrosine kinase inhibitor in humans.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Ffar1 ; Glp-1r ; Insulin Secretion ; Pka ; Sunitinib ; Camp; Pancreatic Beta-cells; Acid Receptor 1; Tyrosine Phosphorylation; In-vitro; Vegf-a; Islets; Mice; Activation; Protects; Death
ISSN (print) / ISBN 0898-6568
e-ISSN 0898-6568
Zeitschrift Cellular Signalling
Quellenangaben Band: 36, Heft: , Seiten: 91-97 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)