| Effects of pharmacological inhibition of NADPH oxidase or iNOS on pro-inflammatory cytokine, palmitic acid or H2O2-induced mouse islet or clonal pancreatic β-cell dysfunction. | |
| | |
MedLine Citation:
|
PMID: 20178457 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Various pancreatic β-cell stressors including cytokines and saturated fatty acids are known to induce oxidative stress, which results in metabolic disturbances and a reduction in insulin secretion. However, the key mechanisms underlying dysfunction are unknown. We investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines, H(2)O(2) or PA (palmitic acid) on β-cell insulin secretion, ATP, the NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) component p47phox and iNOS (inducible nitric oxide synthase) levels using primary mouse islets or clonal rat BRIN-BD11 β-cells. Addition of a pro-inflammatory cytokine mixture [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] or H(2)O(2) (at sub-lethal concentrations) inhibited chronic (24 h) levels of insulin release by at least 50% (from islets and BRIN-BD11 cells), while addition of the saturated fatty acid palmitate inhibited acute (20 min) stimulated levels of insulin release from mouse islets. H(2)O(2) decreased ATP levels in the cell line, but elevated p47phox and iNOS levels as did cytokine addition. Similar effects were observed in mouse islets with respect to elevation of p47phox and iNOS levels. Addition of antioxidants SOD (superoxide dismutase), Cat (catalase) and NAC (N-acetylcysteine) attenuated H(2)O(2) or the saturated fatty acid palmitate-dependent effects, but not cytokine-induced dysfunction. However, specific chemical inhibitors of NADPH oxidase and/or iNOS appear to significantly attenuate the effects of cytokines, H(2)O(2) or fatty acids in islets. While pro-inflammatory cytokines are known to increase p47phox and iNOS levels in β-cells, we now report that H(2)O(2) can increase levels of the latter two proteins, suggesting a key role for positive-feedback redox sensitive regulation of β-cell dysfunction. |
| | |
Authors:
|
Marta Michalska; Gabriele Wolf; Reinhard Walther; Philip Newsholme |
Related Documents
:
|
8244457 - Differential regulation of cytokine production by nitric oxide. 9815217 - Pneumococci stimulate the production of the inducible nitric oxide synthase and nitric ... 11334407 - Tissue inhibitor of metalloproteinase-1 prevents cytokine-mediated dysfunction and cyto... 15290337 - Arginine pathways and the inflammatory response: interregulation of nitric oxide and po... 21784177 - Quantitative determination of the composition of multi-shell calcium phosphate-oligonuc... 8992977 - T cell-derived il-4 and dendritic cell-derived il-12 regulate the lymphokine-producing ... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Bioscience reports Volume: 30 ISSN: 1573-4935 ISO Abbreviation: Biosci. Rep. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-09-27 Completed Date: 2011-01-24 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8102797 Medline TA: Biosci Rep Country: United States |
Other Details:
|
Languages: eng Pagination: 445-53 Citation Subset: IM |
Affiliation:
|
Department of Medical Biochemistry and Molecular Biology, University of Greifswald, D-17487 Greifswald, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenosine Triphosphate
/
metabolism Animals Cell Line Cells, Cultured Cytokines / metabolism, pharmacology* Hydrogen Peroxide / pharmacology* Inflammation / immunology Insulin / secretion Insulin-Secreting Cells / drug effects*, secretion Islets of Langerhans / drug effects*, secretion Mice Mice, Inbred C57BL NADPH Oxidase / antagonists & inhibitors Nitric Oxide Synthase Type II / antagonists & inhibitors Oxidative Stress Palmitic Acid / metabolism, pharmacology* Rats |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 11061-68-0/Insulin; 56-65-5/Adenosine Triphosphate; 57-10-3/Palmitic Acid; 7722-84-1/Hydrogen Peroxide; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sodium tungstate (Na2WO4) exposure increases apoptosis in human peripheral blood lymphocytes.
Next Document: Mesenchymal stem cell infusion therapy in carbon tetrachloride-induced liver fibrosis model affects ...