Linked Life Data

10967113

Source:http://linkedlifedata.com/resource/pubmed/id/10967113

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2000-12-29
pubmed:abstractText
To better understand the action of glucose on fatty acid metabolism in the beta-cell and the link between chronically elevated glucose or fatty acids and beta-cell decompensation in adipogenic diabetes, we investigated whether glucose regulates peroxisomal proliferator-activated receptor (PPAR) gene expression in the beta-cell. Islets or INS(832/13) beta-cells exposed to high glucose show a 60-80% reduction in PPARalpha mRNA expression. Oleate, either in the absence or presence of glucose, has no effect. The action of glucose is dose-dependent in the 6-20 mm range and maximal after 6 h. Glucose also causes quantitatively similar reductions in PPARalpha protein and DNA binding activity of this transcription factor. The effect of glucose is blocked by the glucokinase inhibitor mannoheptulose, is partially mimicked by 2-deoxyglucose, and is not blocked by the 3-O-methyl or the 6-deoxy analogues of the sugar that are not phosphorylated. Chronic elevated glucose reduces the expression levels of the PPAR target genes, uncoupling protein 2 and acyl-CoA oxidase, which are involved in fat oxidation and lipid detoxification. A 3-day exposure of INS-1 cells to elevated glucose results in a permanent rise in malonyl-CoA, the inhibition of fat oxidation, and the promotion of fatty acid esterification processes and causes elevated insulin secretion at low glucose. The results suggest that a reduction in PPARalpha gene expression together with a rise in malonyl-CoA plays a role in the coordinated adaptation of beta-cell glucose and lipid metabolism to hyperglycemia and may be implicated in the mechanism of beta-cell "glucolipotoxicity."
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35799-806
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10967113-Animals, pubmed-meshheading:10967113-Cells, Cultured, pubmed-meshheading:10967113-DNA-Binding Proteins, pubmed-meshheading:10967113-Dose-Response Relationship, Drug, pubmed-meshheading:10967113-Down-Regulation, pubmed-meshheading:10967113-Glucose, pubmed-meshheading:10967113-Insulin, pubmed-meshheading:10967113-Islets of Langerhans, pubmed-meshheading:10967113-Kinetics, pubmed-meshheading:10967113-Malonyl Coenzyme A, pubmed-meshheading:10967113-Models, Biological, pubmed-meshheading:10967113-Oleic Acid, pubmed-meshheading:10967113-Oxidation-Reduction, pubmed-meshheading:10967113-Palmitic Acid, pubmed-meshheading:10967113-Protein Binding, pubmed-meshheading:10967113-RNA, Messenger, pubmed-meshheading:10967113-Rats, pubmed-meshheading:10967113-Rats, Wistar, pubmed-meshheading:10967113-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10967113-Response Elements, pubmed-meshheading:10967113-Transcription Factors, pubmed-meshheading:10967113-Triglycerides
pubmed:year
2000
pubmed:articleTitle
Glucose down-regulates the expression of the peroxisome proliferator-activated receptor-alpha gene in the pancreatic beta -cell.
pubmed:affiliation
Molecular Nutrition Unit, Department of Nutrition, University of Montreal and the Centre Hospitalier de l'Université de Montreal and Institut du Cancer, Montreal, Quebec H2L 4M1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't