title: Chemiluminescence Imaging of Superoxide Anion Detects Beta-Cell Function and Mass.
abstract: Superoxide anion is produced during normal cellular respiration and plays key roles in cellular physiology with its dysregulation being associated with a variety of diseases. Superoxide anion is a short-lived molecule and, therefore, its homeostatic regulation and role in biology and disease requires dynamic quantification with fine temporal resolution. Here we validated coelenterazine as a reporter of intracellular superoxide anion concentration and used it as a dynamic measure both in vitro and in vivo. Chemiluminescence was dependent upon superoxide anion levels, including those produced during cellular respiration, and concentrations varied both kinetically and temporally in response to physiologically relevant fluctuations in glucose levels. In vivo imaging with coelenterazine revealed that beta cells of the pancreas have increased levels of superoxide anion, which acted as a measure of beta-cell function and mass and could predict the susceptibility of mice to diabetes mellitus. Glucose response and regulation are key elements of cellular physiology and organismal biology, and superoxide anion appears to play a fundamental and dynamic role in both of these processes.
authors.affiliation: Department of Biology, Stanford University, 318 Campus Drive, Stanford, California 94305, United States of America.|Department of Pediatrics, Stanford University, 318 Campus Drive, Stanford, California 94305, United States of America.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Bronsart
authors.affiliation: Department of Pediatrics, Stanford University, 318 Campus Drive, Stanford, California 94305, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Stokes
authors.affiliation: Department of Pediatrics, Stanford University, 318 Campus Drive, Stanford, California 94305, United States of America.|Departments of Radiology, Microbiology & Immunology, Stanford University, 318 Campus Drive, Stanford, California 94305, United States of America.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D021621:Imaging, Three-Dimensional; D007093:Imidazoles / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008163:Luminescent Measurements / Q000379:methods*; D016688:Mice, Inbred NOD; D009929:Organ Size / Q000187:drug effects; D011719:Pyrazines / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D000069458:Ranolazine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011719:Pyrazines; D011725:Pyridines; C520311:glucokinase activator compound 50; D013481:Superoxides; C017144:coelenterazine; D000069458:Ranolazine; D005947:Glucose