title: Prevention of oxidative stress by adenoviral overexpression of glutathione-related enzymes in pancreatic islets.
abstract: Chronic exposure to supraphysiologic glucose concentrations causes functional damage to cells and tissues, a process known as glucose toxicity. Recent research indicates that one important mechanism for glucose toxicity is oxidative stress. Glucose has been shown to form reactive oxygen species through several metabolic pathways. The pancreatic islet is distinguished by its relatively low antioxidant enzyme content and activity, which render it especially susceptible to oxidative stress. Adenoviral overexpression of glutathione peroxidase as well as gamma-glutamylcysteine ligase have been shown to protect the islet against oxidative stress. Antioxidants have been shown to brake the worsening of diabetes by improving beta cell function in animal models. These observations suggest that enhancing antioxidant defense mechanisms in pancreatic islets may be a valuable pharmacologic approach to managing diabetes.
authors.affiliation: The Pacific Northwest Research Institute and the University of Washington, 720 Broadway, Seattle, WA 98122, USA. rpr@pnri.org
authors.forename: R Paul
authors.initials: RP
authors.lastname: Robertson
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Phuong Oanh T
authors.initials: PO
authors.lastname: Tran
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Harmon
mesh_terms: D000256:Adenoviridae / Q000201:enzymology*; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000821:virology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005721:Glutamate-Cysteine Ligase; D005947:Glucose