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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2009-10-22
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pubmed:abstractText |
Chronic hyperglycemia causes oxidative stress, which contributes to damage in various tissues and cells, including pancreatic beta-cells. The expression levels of antioxidant enzymes in the islet are low compared with other tissues, rendering the beta-cell more susceptible to damage caused by hyperglycemia. The aim of this study was to investigate whether increasing levels of endogenous glutathione peroxidase-1 (GPx-1), specifically in beta-cells, can protect them against the adverse effects of chronic hyperglycemia and assess mechanisms that may be involved. C57BLKS/J mice overexpressing the antioxidant enzyme GPx-1 only in pancreatic beta-cells were generated. The biological effectiveness of the overexpressed GPx-1 transgene was documented when beta-cells of transgenic mice were protected from streptozotocin. The transgene was then introgressed into the beta-cells of db/db mice. Without use of hypoglycemic agents, hyperglycemia in db/db-GPx(+) mice was initially ameliorated compared with db/db-GPx(-) animals and then substantially reversed by 20 wk of age. beta-Cell volume and insulin granulation and immunostaining were greater in db/db-GPx(+) animals compared with db/db-GPx(-) animals. Importantly, the loss of intranuclear musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) that was observed in nontransgenic db/db mice was prevented by GPx-1 overexpression, making this a likely mechanism for the improved glycemic control. These studies demonstrate that enhancement of intrinsic antioxidant defenses of the beta-cell protects it against deterioration during hyperglycemia.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1945-7170
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
150
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4855-62
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:19819955-Animals,
pubmed-meshheading:19819955-Blood Glucose,
pubmed-meshheading:19819955-Diabetes Mellitus,
pubmed-meshheading:19819955-Disease Models, Animal,
pubmed-meshheading:19819955-Female,
pubmed-meshheading:19819955-Gene Expression,
pubmed-meshheading:19819955-Glutathione Peroxidase,
pubmed-meshheading:19819955-Humans,
pubmed-meshheading:19819955-Hyperglycemia,
pubmed-meshheading:19819955-Insulin-Secreting Cells,
pubmed-meshheading:19819955-Intranuclear Space,
pubmed-meshheading:19819955-Maf Transcription Factors, Large,
pubmed-meshheading:19819955-Male,
pubmed-meshheading:19819955-Mice,
pubmed-meshheading:19819955-Mice, Inbred C57BL,
pubmed-meshheading:19819955-Mice, Transgenic
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pubmed:year |
2009
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pubmed:articleTitle |
beta-Cell-specific overexpression of glutathione peroxidase preserves intranuclear MafA and reverses diabetes in db/db mice.
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pubmed:affiliation |
Pacific Northwest Diabetes Research Institute, 720 Broadway, Seattle, Washington 98122, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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