Glucose Down-regulates the Expression of the Peroxisome Proliferator-activated Receptor-α Gene in the Pancreatic β-Cell *

摘要: Abstract To better understand the action of glucose on fatty acid metabolism in β-cell and link between chronically elevated or acids decompensation adipogenic diabetes, we investigated whether regulates peroxisomal proliferator-activated receptor (PPAR) gene expression β-cell. Islets INS(832/13) β-cells exposed to high show a 60–80% reduction PPARα mRNA expression. Oleate, either absence presence glucose, has no effect. The is dose-dependent 6–20 mm range maximal after 6 h. Glucose also causes quantitatively similar reductions protein DNA binding activity this transcription factor. effect blocked by glucokinase inhibitor mannoheptulose, partially mimicked 2-deoxyglucose, not 3-O-methyl 6-deoxy analogues sugar that are phosphorylated. Chronic reduces levels PPAR target genes, uncoupling 2 acyl-CoA oxidase, which involved fat oxidation lipid detoxification. A 3-day exposure INS-1 cells results permanent rise malonyl-CoA, inhibition oxidation, promotion esterification processes insulin secretion at low glucose. suggest together with malonyl-CoA plays role coordinated adaptation hyperglycemia may be implicated mechanism “glucolipotoxicity.”