| pubmed-article:21533167 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0001779 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0030274 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0021641 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C1171362 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0441889 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C1826562 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0547047 | lld:lifeskim |
| pubmed-article:21533167 | lifeskim:mentions | umls-concept:C0910022 | lld:lifeskim |
| pubmed-article:21533167 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:21533167 | pubmed:dateCreated | 2011-5-2 | lld:pubmed |
| pubmed-article:21533167 | pubmed:abstractText | Advanced glycation end products (AGEs) have been implicated in diverse pathological settings of many diabetic complications, and the possible mechanisms have been widely reported. However, the relationship between AGEs and pancreatic ?-cell dysfunction is still poorly understood. Recent studies have shown that AGEs can impair ?-cell function by inducing apoptosis or decreasing insulin secretion. Our previous research revealed that AGEs could significantly down-regulate insulin transcription and reduce ?-cell glucose-stimulated insulin secretion (GSIS). Here, we investigated the possible mechanisms underlying AGE-related suppression of insulin synthesis. In the rat pancreatic ?-cell line INS-1, we found that AGEs induced dephosphorylation of Foxo1 and increased its accumulation in the nucleus. The translocation of Foxo1 subsequently inhibited pancreatic-duodenal homeobox factor-1 (Pdx-1) levels in both nuclear and cytoplasmic compartments. We observed that with AGEs treatment, Pdx-1 protein levels decreased after 4 h, but there was no change in the Pdx-1 mRNA level or promoter activity at the same time point; this demonstrated that the decrease in Pdx-1 expression was not regulated at the transcriptional level. In our study, the decrease in Pdx-1 protein level was related to its reduced stability, overexpression of DN-Foxo1 could partially reverse the inhibition of Pdx-1 expression. Pretreatment with AGEs receptor (RAGE) antibody also prevented the AGE-induced diminution of Pdx-1 protein and insulin mRNA expression. In summary, AGEs induced nuclear accumulation of Foxo1; this in turn reduced Pdx-1 expression by decreasing its protein stability, ultimately affecting insulin synthesis. | lld:pubmed |
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| pubmed-article:21533167 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21533167 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21533167 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21533167 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21533167 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21533167 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21533167 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21533167 | pubmed:issn | 1932-6203 | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:OrrV BVB | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:HanXiaoX | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:MaZhuoZ | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:ZhuYunxiaY | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:WangHongdongH | lld:pubmed |
| pubmed-article:21533167 | pubmed:author | pubmed-author:ShuTingtingT | lld:pubmed |
| pubmed-article:21533167 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21533167 | pubmed:volume | 6 | lld:pubmed |
| pubmed-article:21533167 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21533167 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21533167 | pubmed:pagination | e18782 | lld:pubmed |
| pubmed-article:21533167 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:21533167 | pubmed:meshHeading | pubmed-meshheading:21533167... | lld:pubmed |
| pubmed-article:21533167 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21533167 | pubmed:articleTitle | AGEs decrease insulin synthesis in pancreatic ?-cell by repressing Pdx-1 protein expression at the post-translational level. | lld:pubmed |
| pubmed-article:21533167 | pubmed:affiliation | Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China. | lld:pubmed |
| pubmed-article:21533167 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21533167 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:29535 | entrezgene:pubmed | pubmed-article:21533167 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21533167 | lld:entrezgene |
