title: Oxidative stress and beta cell dysfunction.
abstract: Autoimmune Type 1 A Diabetes (T1D) is characterized by dependence on exogenous insulin consequential to the autoimmune attack and destruction of insulin-producing islet beta cells. Pancreatic islet cell inflammation, or insulitis, precedes beta cell death and T1D onset. In the insulitic lesion, innate immune cells produce chemokines and cytokines that recruit and activate adaptive immune cells (Eizirik D et al., Nat Rev Endocrinol 5:219-226, 2009). Locally produced cytokines not only increase immune surveillance of beta cells (Hanafusa T and Imagawa A, Ann NY Acad Sci 1150:297-299, 2008), but also cause beta cell dysfunction and decreased insulin secretion due to the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by the beta cells. This, coupled to the high levels of ROS and RNS secreted by activated macrophages and the low antioxidant capacities of beta cells (Huurman VA, PLoS One 3:e2435, 2008; Schatz D, Pediatr Diabetes 5:72-79, 2004; Verge CF, Diabetes 44:1176-1179, 1995), implicates free radicals as important effectors in T1D pathogenesis (Eizirik D et al., Nat Rev Endocrinol 5:219-226, 2009; Hanafusa T and Imagawa A, Ann NY Acad Sci 1150:297-299, 2008; Eisenbarth GS and Jeffrey J, Arq Bras Endocrinol Metabol 52:146-155, 2008; Pietropaolo M et al., Pediatr Diabetes 6:184-192, 2005).
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Yaíma L
authors.initials: YL
authors.lastname: Lightfoot
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Clayton E
authors.initials: CE
authors.lastname: Mathews
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020169:Caspases / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D057075:Enzyme Assays; D005978:Glutathione / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D020169:Caspases; D005978:Glutathione