title: Relationship of NADPH Oxidase-1 expression to beta cell dysfunction induced by inflammatory cytokines.
abstract: Redox stress related loss of beta cell function is a feature of diabetes. Exposure of beta cells and islets to inflammatory mediators elevates reactive oxygen species (ROS) and beta cell dysfunction. Direct molecular manipulation of NADPH oxidase-1 (NOX-1) has identified a key role for NOX-1 in cytokine-induced beta cell dysfunction. Plasmid driven elevation of NOX-1 resulted in elevated ROS, loss of glucose-stimulated-insulin-secretion and increased apoptosis. These outcomes on beta cell function are analogous to cytokine treatment. In contrast, reduction of NOX-1 expression, by shRNA, conferred protection to beta cells and islets from the damaging effects of inflammatory cytokines. Collectively, these data support the therapeutic potential for NOX-1 inhibition in diabetes.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Weaver
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: taylord@evms.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Taylor-Fishwick
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000074624:NADPH Oxidase 1; D018384:Oxidative Stress; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D007328:Insulin; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D005947:Glucose
keywords: Beta cell function; Diabetes; Inflammation; NADPH oxidase; Protein expression; Reactive oxygen species