pubmed-article:12031966 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0227525 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0030274 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0521447 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0202220 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C1414685 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
pubmed-article:12031966 | lifeskim:mentions | umls-concept:C1998811 | lld:lifeskim |
pubmed-article:12031966 | pubmed:issue | 6 | lld:pubmed |
pubmed-article:12031966 | pubmed:dateCreated | 2002-5-28 | lld:pubmed |
pubmed-article:12031966 | pubmed:abstractText | Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant- negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [(3)H]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with noninduced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3. | lld:pubmed |
pubmed-article:12031966 | pubmed:language | eng | lld:pubmed |
pubmed-article:12031966 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:citationSubset | AIM | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12031966 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12031966 | pubmed:month | Jun | lld:pubmed |
pubmed-article:12031966 | pubmed:issn | 0012-1797 | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:MatsuzawaYuji... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:YamagataKazuy... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:WollheimClaes... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:WangHaiyanH | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:NammoTakaoT | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:YangQinQ | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:IwahashiHirom... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:CaoYangY | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:HanafusaToshi... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:BucalaRichard... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:MatsumuraItar... | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:FukuiKenjiK | lld:pubmed |
pubmed-article:12031966 | pubmed:author | pubmed-author:MiyagawaJun-I... | lld:pubmed |
pubmed-article:12031966 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:12031966 | pubmed:volume | 51 | lld:pubmed |
pubmed-article:12031966 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:12031966 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:12031966 | pubmed:pagination | 1785-92 | lld:pubmed |
pubmed-article:12031966 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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pubmed-article:12031966 | pubmed:year | 2002 | lld:pubmed |
pubmed-article:12031966 | pubmed:articleTitle | Hepatocyte nuclear factor-1alpha modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells. | lld:pubmed |
pubmed-article:12031966 | pubmed:affiliation | Department of Internal Medicine and Molecular Science, Biomedical Research Center, Graduate School of Medicine, Osaka University, Osaka, Japan. | lld:pubmed |
pubmed-article:12031966 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:12031966 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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