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http://purl.uniprot.org/citations/15739117http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15739117http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Hyperglycaemia and the pro-inflammatory cytokine IL-1beta induce similar alterations of beta cell gene expression, including up-regulation of c-Myc and haeme-oxygenase 1. These effects of hyperglycaemia may result from nuclear factor-kappa B (NFkappaB) activation by oxidative stress. To test this hypothesis, we compared the effects of IL-1beta, high glucose, and hydrogen peroxide, on NFkappaB DNA binding activity and target gene mRNA levels in cultured rat islets.

Methods

Rat islets were pre-cultured for 1 week in serum-free RPMI medium containing 10 mmol/l glucose, and further cultured in glucose concentrations of 5-30 mmol/l plus various test substances. Islet NFkappaB activity was measured by ELISA and gene mRNA expression was measured by RT-PCR.

Results

IL-1beta consistently increased islet NFkappaB activity and c-Myc, haeme-oxygenase 1, inducible nitric oxide synthase (iNOS), Fas, and inhibitor of NFkappaB alpha (IkappaBalpha) mRNA levels. In comparison, 1-to 7-day culture in 30 mmol/l instead of 10 mmol/l glucose stimulated islet c-Myc and haeme-oxygenase 1 expression without affecting NFkappaB activity or iNOS and IkappaBalpha mRNA levels. Fas mRNA levels only increased after 1 week in 30 mmol/l glucose. Overnight exposure to hydrogen peroxide mimicked the effects of 30 mmol/l glucose on haeme-oxygenase 1 and c-Myc mRNA levels without activating NFkappaB. On the other hand, the antioxidant N-acetyl-L-cysteine inhibited the stimulation of haeme-oxygenase 1 and c-Myc expression by 30 mmol/l glucose and/or hydrogen peroxide.

Conclusions/interpretation

In contrast to IL-1beta, high glucose and hydrogen peroxide do not activate NFkappaB in cultured rat islets. It is suggested that the stimulation of islet c-Myc and haeme-oxygenase 1 expression by 30 mmol/l glucose results from activation of a distinct, probably oxidative-stress-dependent signalling pathway."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.org/dc/terms/identifier"doi:10.1007/s00125-004-1664-4"xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/author"Jonas J.C."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/author"Eizirik D.L."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/author"Henquin J.C."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/author"Cardozo A.K."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/author"Elouil H."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/pages"496-505"xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/title"High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NFkappaB."xsd:string
http://purl.uniprot.org/citations/15739117http://purl.uniprot.org/core/volume"48"xsd:string
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