Studies on the molecular regulation of the inducible form of nitric oxide synthase (iNOS) in insulin-producing cells.
Nitric oxide, a radical generated by the enzyme nitric oxide synthase (iNOS), may be an important mediator of beta-cell damage in early insulin-dependent diabetes mellitus. We have investigated the molecular regulation of iNOS in insulin-producing RINm5F cells. The data obtained suggest that iNOS is maximally induced in these cells by a 6-h exposure to IL-1 beta or TNF-alpha + IFN-gamma, but not by endotoxin. iNOS mRNA degradation is rapid and it is not affected by IL-1 beta. Interestingly, NO seems to induce a negative feedback on iNOS expression, probably by decreasing iNOS transcription.
Niemann
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Department of Medical Cell Biology, Uppsala University, Sweden.
Björklund
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Eizirik
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D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007340:Insulinoma / Q000201:enzymology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases