Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1.
Diabetes
; 48(10): 2007-14, 1999 Oct.
Article
em En
| MEDLINE
| ID: mdl-10512366
ABSTRACT
To better understand the link between fatty acid signaling and the pleiotropic effects of fatty acids in the pancreatic beta-cell, we investigated whether fatty acids regulate immediate-early response genes (IEGs) coding for transcription factors implicated in cell proliferation, differentiation, and apoptosis. Palmitate and oleate, but not long-chain polyunsaturated fatty acids, caused a pronounced accumulation of c-fos and nur-77 mRNAs in beta-cells (INS cells) to an extent similar to that produced by the protein kinase C (PKC) activator phorbol myristate acetate (PMA). The effect was dose dependent and occurred at concentrations between 0.1 and 0.5 mmol/l in the presence of 0.5% albumin. The action of the fatty acid occurred at the transcriptional level, and the mRNA accumulation displayed a bell-shaped kinetics with a maximal effect at 1 h. 2-Bromopalmitate was ineffective, indicating that fatty acids must be metabolized to cause their effect. Neither fatty acid was able to induce c-fos and nur-77 in PKC-downregulated cells or cells incubated in the presence of the Ca2+ channel blocker nifedipine or the Ca2+ chelator EGTA, suggesting involvement of the PKC and Ca2+ signaling pathways. Palmitate and oleate also increased c-fos protein expression and DNA binding activity of the transcription factor AP-1. Oleate, but not palmitate, increased [3H]thymidine incorporation in INS cells. Finally, both palmitate and oleate caused c-fos and nur-77 mRNA accumulation in isolated rat islets. It is suggested that IEG induction by the most abundant circulating fatty acids plays a role in the adaptive process of the beta-cell to hyperlipidemia. These results have implications for our understanding of obesity-associated diabetes and the link between fatty acids and tumorigenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Palmitatos
/
Fatores de Transcrição
/
Receptores de Esteroides
/
Ilhotas Pancreáticas
/
Proteínas Proto-Oncogênicas c-fos
/
Receptores Citoplasmáticos e Nucleares
/
Ácido Oleico
/
Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Espanha