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(4): 1537-45, 2015.
Article
em En
| MEDLINE
| ID: mdl-25792236
ABSTRACT
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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Base de dados:
MEDLINE
Assunto principal:
Palmitatos
/
Apoptose
/
Proteína Quinase 1 Ativada por Mitógeno
/
Receptores Acoplados a Proteínas G
/
Proteína Quinase 3 Ativada por Mitógeno
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article