| pubmed-article:20855893 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0330390 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0030274 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0001962 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0017713 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0277785 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0013081 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C1328815 | lld:lifeskim |
| pubmed-article:20855893 | lifeskim:mentions | umls-concept:C0205191 | lld:lifeskim |
| pubmed-article:20855893 | pubmed:issue | 48 | lld:pubmed |
| pubmed-article:20855893 | pubmed:dateCreated | 2010-11-24 | lld:pubmed |
| pubmed-article:20855893 | pubmed:abstractText | Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of chronic ethanol consumption on pancreatic ?-cell dysfunction and whether generated peroxynitrite participates in the impaired glucose homeostasis. Here we show that chronic ethanol feeding decreases the ability of pancreatic ?-cells to mediate insulin secretion and ATP production in coordination with the decrease of glucokinase, Glut2, and insulin expression. Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(?C) attenuated ethanol-induced pancreatic ?-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol. GCK inactivation and down-regulation were predominantly mediated by ethanol metabolism-generated peroxynitrite, which were suppressed by the peroxynitrite scavengers N(?)-monomethyl-L-arginine, uric acid, and deferoxamine but not by the S-nitrosylation inhibitor DTT, indicating that tyrosine nitration is the predominant modification associated with GCK down-regulation and inactivation rather than S-nitrosylation of cysteine. Tyrosine nitration of GCK prevented its association with pBad, and GCK translocation into the mitochondria results in subsequent proteasomal degradation of GCK following ubiquitination. This study identified a novel and efficient pathway by which chronic ethanol consumption may induce GCK down-regulation and inactivation by inducing tyrosine nitration of GCK, resulting in pancreatic ?-cell apoptosis and dysfunction. Peroxynitrite-induced ATF3 may also serve as a potent upstream regulator of GCK down-regulation and ?-cell apoptosis. | lld:pubmed |
| pubmed-article:20855893 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20855893 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20855893 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20855893 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:20855893 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:KimDae JinDJ | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:KimWon-HoWH | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:LeeInkyuI | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:LeeHyun... | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:KimJi YeonJY | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:SongJihyunJ | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:ParkYoon... | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:ParkJoo-WonJW | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:OhYeo... | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:KimBong JoBJ | lld:pubmed |
| pubmed-article:20855893 | pubmed:author | pubmed-author:SongEun... | lld:pubmed |
| pubmed-article:20855893 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20855893 | pubmed:day | 26 | lld:pubmed |
| pubmed-article:20855893 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:20855893 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20855893 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20855893 | pubmed:pagination | 37251-62 | lld:pubmed |
| pubmed-article:20855893 | pubmed:dateRevised | 2011-1-6 | lld:pubmed |
| pubmed-article:20855893 | pubmed:meshHeading | pubmed-meshheading:20855893... | lld:pubmed |
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| pubmed-article:20855893 | pubmed:meshHeading | pubmed-meshheading:20855893... | lld:pubmed |
| pubmed-article:20855893 | pubmed:meshHeading | pubmed-meshheading:20855893... | lld:pubmed |
| pubmed-article:20855893 | pubmed:meshHeading | pubmed-meshheading:20855893... | lld:pubmed |
| pubmed-article:20855893 | pubmed:meshHeading | pubmed-meshheading:20855893... | lld:pubmed |
| pubmed-article:20855893 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20855893 | pubmed:articleTitle | Chronic ethanol consumption-induced pancreatic {beta}-cell dysfunction and apoptosis through glucokinase nitration and its down-regulation. | lld:pubmed |
| pubmed-article:20855893 | pubmed:affiliation | Divisions of Metabolic Diseases, National Institutes of Health, Eunpyeong-gu, Seoul 122-701, Korea. | lld:pubmed |
| pubmed-article:20855893 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20855893 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:103988 | entrezgene:pubmed | pubmed-article:20855893 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:20855893 | lld:entrezgene |
