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The Effect of Chronic Exposure to Fatty Acids on Gene Expression in Clonal Insulin-Producing Cells: Studies Using High Density Oligonucleotide Microarray

Department of Endocrinology and Metabolism C, Aarhus University Hospital (J.X., S.G., K.H.), 8000 Aarhus C, Denmark; and Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital (M.K., T.F.O.), 8200 Aarhus N, Denmark

Address all correspondence and requests for reprints to: Kjeld Hermansen, M.D., Department of Endocrinology and Metabolism C, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. E-mail: kjeld.hermansen{at}dadlnet.dk

Fatty acids affect insulin secretion of pancreatic ß-cells. Investigating gene expression profiles may help to characterize the underling mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 µM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We found that basal insulin secretion increased in cells exposed to palmitate. The response to glucose stimulation declined on d 44 in cells cultured at 200 µM palmitate. In response to 50 and 200 µM palmitate exposure, expression was changed in 11 and 99 genes on d 2 and 134 and in 159 genes on d 44, respectively. Genes involved in fatty acid oxidation were up-regulated, whereas those involved in glycolysis were down-regulated with 200 µM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 µM palmitate. In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle’s fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression of various genes may contribute to the functional changes.

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