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

Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We f...

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Published inEndocrinology (Philadelphia) Vol. 142; no. 11; p. 4777
Main Authors Xiao, J, Gregersen, S, Kruhøffer, M, Pedersen, S B, Ørntoft, T F, Hermansen, K
Format Journal Article
LanguageEnglish
Published United States 01.11.2001
Subjects
Cell Line
Clone Cells - drug effects
Clone Cells - metabolism
Drug Synergism
Fatty Acids - pharmacology
Gene Expression - drug effects
Glucose - pharmacology
Insulin - biosynthesis
Oligonucleotide Array Sequence Analysis
Palmitates - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
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Summary:Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) 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 microM palmitate. In response to 50 and 200 microM 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 microM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 microM 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.
ISSN:0013-7227
DOI:10.1210/en.142.11.4777