Role of increased ROS dissipation in prevention of T1D.
Protection of pancreatic beta cells is an approach to prevent autoimmune type 1 diabetes (T1D) and to protect transplanted islets. Reactive oxygen species (ROS) are important mediators of beta cell death during the development of T1D. We have examined the role of elevated ROS dissipation in the prevention of T1D using the ALR mouse strain. The selection of ALR, for resistance against alloxan-induced free radical-mediated diabetes, led to a strain of mice with an elevated systemic as well as pancreatic ROS dissipation. Independent genetic mapping studies have identified ALR-derived diabetes protective loci. Conplastic and congenic mouse as well as cell line studies have confirmed the genetic mapping and demonstrated that the elevated ROS dissipation protects ALR beta cells from autoimmune destruction. Our data support the hypothesis that elevated ROS dissipation protects beta cells against autoimmune destruction and prevents T1D development.
Chen
Jing
J
Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610-0275, USA.
Gusdon
Aaron M
AM
Thayer
Terri C
TC
Mathews
Clayton E
CE
D000496:Alloxan; D000818:Animals; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology
D017382:Reactive Oxygen Species; D000496:Alloxan