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Panse, M.* ; Gerst, F. ; Kaiser, G. ; Teutsch, C.A.* ; Dölker, R.* ; Wagner, R. ; Häring, H.-U. ; Ullrich, S.

Activation of Extracellular signal-Regulated protein Kinases 1 and 2 (ERK1/2) by Free Fatty Acid Receptor 1 (FFAR1/GPR40) protects from palmitate-induced beta cell death, but plays no role in insulin secretion.

Cell. Physiol. Biochem. 35, 1537-1545 (2015)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
AIMS: GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death. METHODS: Insulin secretion of INS-1E cells was measured by radioimmunoassay. Protein phosphorylation was examined on Western blots. Apoptosis was assessed by TUNEL staining. RESULTS: Palmitate and the GPR40/FFAR1 agonist TUG-469 increased phosphorylation of ERK1/2 at low (2.8 mmol/L) and high (12 mmol/L) glucose but stimulated insulin secretion only at high glucose. The MEK1 inhibitor PD98059 significantly reduced phosphorylation of ERK1/2 but did not reverse the stimulation of secretion induced by glucose, palmitate or TUG-469. PD98059 rather augmented glucose-induced secretion. Prolonged exposure to palmitate stimulated apoptosis, an effect counteracted by TUG-469. PD98059 accentuated palmitate-induced apoptosis and reversed TUG-469-mediated inhibition of cell death. CONCLUSIONS: Activation of ERK1/2 by palmitate and GPR40/FFAR1 agonist correlates neither with stimulation of insulin secretion nor with induction of apoptosis. The results suggest a significant anti-apoptotic role of ERK1/2 under conditions of lipotoxicity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Fatty Acid Receptor-1 ; Gpr40/ffar1 ; Insulin Secretion ; Beta-cell Apoptosis ; Erk1/2 ; Lipotoxicity; Gene-expression; Er Stress; Apoptosis; Pathway; Glucose; Gpr40; Line; Min6; Phosphorylation; Stimulation
ISSN (print) / ISBN 1015-8987
e-ISSN 1421-9778
Zeitschrift Cellular Physiology and Biochemistry
Quellenangaben Band: 35, Heft: 4, Seiten: 1537-1545 Artikelnummer: , Supplement: ,
Verlag Karger
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)