Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 10; pp. 2007 - 2014
• Main Authors: ROCHE, E, BUTEAU, J, ANIENTO, I, REIG, J. A, SORIA, B, PRENTKI, M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.1999
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cell proliferation; Cellular signal transduction; DNA - metabolism; DNA-Binding Proteins - genetics; Endocrine pancreas; Fatty acid metabolism; Fundamental and applied biological sciences. Psychology; Glucose - pharmacology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Isoenzymes - metabolism; Kinetics; Morphology. Functional localizations; Nuclear Receptor Subfamily 4, Group A, Member 1; Oleic Acid - pharmacology; Palmitates - pharmacology; Physiological aspects; Protein Kinase C - metabolism; Proto-Oncogene Proteins c-fos - genetics; Rats; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Steroid - genetics; RNA, Messenger - metabolism; Transcription Factor AP-1 - metabolism; Transcription Factors - genetics; Transcription, Genetic; Vertebrates: endocrinology; Cell proliferation; Langerhans islet; Lipids; Palmitic acid; Fatty acids; Cell line; B-Cell; Oleic acid; Differentiation; Protooncogene; Endocrine pancreas; Apoptosis; Immediate early gene
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.10.2007

Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1. E Roche , J Buteau , I Aniento , J A Reig , B Soria and M Prentki Instituto de Bioingeniería/Division of Nutrition, University Miguel Hernández, Alicante, Spain. 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.