| Knockouts of SOD1 and GPX1 exert different impacts on murine islet function and pancreatic integrity. | |
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MedLine Citation:
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PMID: 20586612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Metabolic subtlety and clinical relevance of different forms of reactive oxygen species in diabetes remain unclear. Using single knockout of Cu,Zn-superoxide dismutase (SOD1(-/-)) or Se-glutathione peroxidase-1 (GPX1(-/-)) and their double-knockout (DKO) mouse models, we determined if elevating endogenously-derived superoxide and hydroperoxide exerted distinct impacts and mechanisms on body glucose homeostasis. Whereas the three knockout groups displayed decreased plasma insulin concentrations and islet β-cells mass, only SOD1(-/-) showed decreased body weight, increased blood glucose, and blocked glucose-stimulated insulin secretion. Null of SOD1 and GPX1 elevated respective islet superoxide and hydroperoxide production, and upregulated p53 phosphorylation. Knockout of SOD1 downregulated the foxhead box A2/pancreatic and duodenal homeobox 1 pathway in a superoxide-dependent fashion at epigenetic, mRNA, and protein levels in islets, but improved insulin signaling in liver and muscle. The SOD1(-/-) mice showed more apparent pancreatitis than the GPX1(-/-) mice that were more susceptible to the cerulein-induced amylase increase. Knockout of SOD1 impaired islet function, pancreas integrity, and body glucose homeostasis more than that of GPX1. Simultaneous ablation of both enzymes did not result in additive or aggravated metabolic outcomes. |
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Authors:
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Xiaodan Wang; Marko Z Vatamaniuk; Carol A Roneker; Matthew P Pepper; Liangbiao G Hu; Rebecca A Simmons; Xin Gen Lei |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-29 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 14 ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-05 Completed Date: 2011-04-14 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 391-401 Citation Subset: IM |
Affiliation:
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Department of Animal Science, Cornell University, Ithaca, New York 14853, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Epigenesis, Genetic Gene Expression Regulation Glutathione Peroxidase / genetics, metabolism* Hepatocyte Nuclear Factor 3-beta / genetics, metabolism Homeostasis Hydrogen Peroxide / metabolism Insulin / metabolism Islets of Langerhans / physiology* Mice Mice, Inbred C57BL Mice, Knockout* Pancreas / anatomy & histology, physiology*, physiopathology Phenotype Reactive Oxygen Species / metabolism Signal Transduction / physiology Superoxide Dismutase / genetics, metabolism* Superoxides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK53018/DK/NIDDK NIH HHS; DK55704/DK/NIDDK NIH HHS; R01 DK053018-11/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Foxa2 protein, mouse; 0/Insulin; 0/Reactive Oxygen Species; 11062-77-4/Superoxides; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.-/glutathione peroxidase GPX1; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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