The effect of chronic exposure to fatty acids on gene expression in clonalinsulin-producing cells: Studies using high density oligonucleotide microarray

Fatty acids affect insulin secretion of pancreatic P-cells. Investigating g ene expression profiles may help to characterize the underling mechanism. I NS-1 cells were cultured with palmitate (0, 50, and 200 muM) for up to 44 d . Insulin secretion and expressions of 8740 genes were studied. We found th at basal insulin secretion increased in cells exposed to palmitate. The res ponse to glucose stimulation declined on d 44 in cells cultured at 200 mum palmitate. In response to 50 and 200 mum palmitate exposure, expression was changed in 11 and 99 genes on d 2 and 134 and in 159 genes on d 44, respec tively. Genes involved in fatty acid oxidation were up-regulated, whereas t hose involved in glycolysis were down-regulated with 200 mum palmitate. A s uppression of insulin receptor and insulin receptor substate-2 gene express ion was found on d 44 in cells cultured at 200 mum palmitate. In conclusion , chronic exposure to low palmitate alters insulin secretion as well as gen e expression. The number of genes that changed expression was palmitate dos e and exposure time dependent. Randle's fatty acid-glucose cycle seems to b e operative on the gene transcription level. A modification of expression o f various genes may contribute to the functional changes.