| Two tales of antioxidant enzymes on β cells and diabetes. | |
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MedLine Citation:
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PMID: 20618069 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pancreatic islets contain low activities of catalase, selenium-dependent glutathione peroxidase 1 (GPX1), and Cu,Zn-superoxide dismutase 1 (SOD1). Thus, enhancing expression of these enzymes in islets has been unquestionably favored. However, such an attempt has produced variable metabolic outcomes. While β cell-specific overexpression of Sod1 enhanced mouse resistance to streptozotocin-induced diabetes, the same manipulation of catalase aggravated onset of type 1 diabetes in nonobese diabetic mice. Global overexpression of Gpx1 in mice induced type 2 diabetes-like phenotypes. Although knockouts of Gpx1 and Sod1 each alone or together decreased pancreatic β cell mass and plasma insulin concentrations, these knockouts improved body insulin sensitivity to different extents. Pancreatic duodenal homeobox 1, forkhead box A2, and uncoupling protein 2 are three key regulators of β cell mass, insulin synthesis, and glucose-stimulated insulin secretion. Phenotypes resulted from altering GPX1 and/or SOD1 were partly mediated through these factors, along with protein kinase B and c-jun terminal kinase. A shifted reactive oxygen species inhibition of protein tyrosine phosphatases in insulin signaling might be attributed to altered insulin sensitivity. Overall, metabolic roles of antioxidant enzymes in β cells and diabetes depend on body oxidative status and target functions. Revealing regulatory mechanisms for this type of dual role will help prevent potential pro-diabetic risk of antioxidant over-supplementation to humans. |
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Authors:
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Xin Gen Lei; Marko Z Vatamaniuk |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2010-10-19 |
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: 489-503 Citation Subset: IM |
Affiliation:
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Department of Animal Science, Cornell University, Ithaca, New York 14853, USA. XL20@cornell.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / metabolism* Catalase / metabolism Diabetes Mellitus, Type 1 / enzymology*, physiopathology Glucose / metabolism Glutathione Peroxidase / metabolism Hepatocyte Nuclear Factor 3-beta / metabolism Homeodomain Proteins / metabolism Humans Insulin / metabolism Insulin-Secreting Cells / enzymology* Ion Channels / metabolism Mitochondrial Proteins / metabolism Oxidative Stress Reactive Oxygen Species / metabolism Signal Transduction / physiology Superoxide Dismutase / metabolism Trans-Activators / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK53018/DK/NIDDK NIH HHS; R01 DK053018-11/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Homeodomain Proteins; 0/Insulin; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 0/Trans-Activators; 0/mitochondrial uncoupling protein 2; 0/pancreatic and duodenal homeobox 1 protein; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 50-99-7/Glucose; EC 1.11.1.-/glutathione peroxidase GPX1; EC 1.11.1.6/Catalase; 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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