title: β-Cell responses to nitric oxide.
abstract: Autoimmune diabetes is characterized by the selective destruction of insulin-secreting β-cells that occurs during an inflammatory reaction in and around pancreatic islets of Langerhans. Cytokines such as interleukin-1, released by activated immune cells, have been shown to inhibit insulin secretion from pancreatic β-cells and cause islet destruction. In response to cytokines, β-cells express inducible nitric oxide synthase and produce micromolar levels of the free radical nitric oxide. Nitric oxide inhibits the mitochondrial oxidation of glucose resulting in an impairment of insulin secretion. Nitric oxide is also responsible for cytokine-mediated DNA damage in β-cells. While nitric oxide mediates the inhibitory and toxic effects of cytokines, it also activates protective pathways that allow β-cells to recover from this damage. This review will focus on the dual role of nitric oxide as a mediator of cytokine-induced damage and the activator of repair mechanisms that protect β-cells from cytokine-mediated injury.
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Broniowska
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Bryndon J
authors.initials: BJ
authors.lastname: Oleson
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address: jcorbett@mcw.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Corbett
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Cytokines; Inducible nitric oxide synthase; Nitric oxide; Type-1 diabetes