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Null of Se‐glutathione peroxidase‐1 (GPX1) or Cu, Zn‐superoxide dismutase (SOD1) suppresses murine pancreatic insulin synthesis and secretion
Author(s) -
Wang Xiaodan,
Vatamaniuk Marko Z.,
Roneker Carol A.,
Lei Xin Gen
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.146.4
Subject(s) - medicine , endocrinology , gpx1 , sod1 , insulin , pancreatic islets , chemistry , superoxide dismutase , glutathione peroxidase , islet , biology , oxidative stress
Physiological roles of antioxidant enzymes in body insulin metabolism still remain elusive. We compared impacts of null of GPX1 and SOD1 alone or in combination on pancreatic insulin synthesis, secretion, and function. Male mice (8‐wk old) of GPX1 null (GPX1−/−), SOD1 null (SOD1−/−), double knockout of both enzymes (DKO), and their wild‐type (WT) were fed a Se‐adequate diet and used for various tests (n = 6 per genotype by assay). Compared with the WT, the 3 knockout groups exhibited lower (P < 0.05) pancreatic β cell mass (44 to 59%), plasma insulin concentration (46 to 68%), glucose stimulated insulin secretion in cultured islets and plasma (27 to 79%), and ATP production in islets (52 to 67%), along with elevated (P < 0.05) hydroperoxide production in islets. However, these 3 null groups had glucose tolerance similar to the WT. Despite showing a higher (P < 0.05) fasted blood glucose concentration, the SOD1−/− actually had improved insulin tolerance over the WT. Although both GPX1−/− and SOD1−/− islets had elevated phosphor‐p53 and phosphor‐p38 MAPK protein levels than the WT, only the SOD1−/− islets showed lower (P < 0.05) mRNA and protein levels of pancreatic duodenal homeobox‐1 and its upstream regulator forkhead protein a2. In conclusion, null of SOD1 exerted more pronounced impact on pancreatic insulin metabolism and function than that of GPX1, and the DKO did not worsen the scenario. [NIH DK 53018 to XGL]