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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
34
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pubmed:dateCreated |
2009-8-26
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pubmed:abstractText |
Maturity-onset diabetes of the young (MODY) is a subtype of diabetes defined by an autosomal pattern of inheritance and a young age at onset, often before age 25. MODY is genetically heterogeneous, with 8 distinct MODY genes identified to date and more believed to exist. We resequenced 732 kb of genomic sequence at 8p23 in 6 MODY families unlinked to known MODY genes that showed evidence of linkage at that location. Of the 410 sequence differences that we identified, 5 had a frequency <1% in the general population and segregated with diabetes in 3 of the families, including the 2 showing the strongest support for linkage at this location. The 5 mutations were all placed within 100 kb corresponding to the BLK gene. One resulted in an Ala71Thr substitution; the other 4 were noncoding and determined decreased in vitro promoter activity in reporter gene experiments. We found that BLK--a nonreceptor tyrosine-kinase of the src family of proto-oncogenes--is expressed in beta-cells where it enhances insulin synthesis and secretion in response to glucose by up-regulating transcription factors Pdx1 and Nkx6.1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-10545951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-10648608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-10793008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-11596660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-12453976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-12882939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-15111509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-15774581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-15883383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-16297379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-16369531,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-16449388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-18073315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-18204098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-18347054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-18372903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-2163307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-2404338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-2877024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-4212169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-8433729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-8945470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-8945471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-9326926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-9398836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19667185-9560151
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:Bonner-WeirSusanS,
pubmed-author:BoonyasrisawatWatipW,
pubmed-author:BorowiecMaciejM,
pubmed-author:DoriaAlessandroA,
pubmed-author:El KhattabiIlhamI,
pubmed-author:HuJiangJ,
pubmed-author:KimSung-HoonSH,
pubmed-author:KrolewskiAndrzej SAS,
pubmed-author:KulkarniRohit NRN,
pubmed-author:LiewChong WCW,
pubmed-author:MarselliLorellaL,
pubmed-author:MlynarskiWojciech MWM,
pubmed-author:MychaleckyjJosyf CJC,
pubmed-author:RichStephen SSS,
pubmed-author:SalaMichelaM,
pubmed-author:SharmaArunA,
pubmed-author:ThompsonRyanR
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14460-5
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19667185-Humans,
pubmed-meshheading:19667185-Animals,
pubmed-meshheading:19667185-Adolescent,
pubmed-meshheading:19667185-Insulin,
pubmed-meshheading:19667185-Mutation,
pubmed-meshheading:19667185-Luciferases,
pubmed-meshheading:19667185-Female,
pubmed-meshheading:19667185-Male,
pubmed-meshheading:19667185-Adult,
pubmed-meshheading:19667185-Middle Aged,
pubmed-meshheading:19667185-Insulin-Secreting Cells,
pubmed-meshheading:19667185-Young Adult,
pubmed-meshheading:19667185-Pedigree,
pubmed-meshheading:19667185-Family Health,
pubmed-meshheading:19667185-Genetic Predisposition to Disease,
pubmed-meshheading:19667185-Diabetes Mellitus, Type 2,
pubmed-meshheading:19667185-Cell Line, Tumor,
pubmed-meshheading:19667185-Recombinant Fusion Proteins,
pubmed-meshheading:19667185-Blotting, Western,
pubmed-meshheading:19667185-DNA Mutational Analysis,
pubmed-meshheading:19667185-src-Family Kinases,
pubmed-meshheading:19667185-Microscopy, Confocal,
pubmed-meshheading:19667185-Reverse Transcriptase Polymerase Chain Reaction
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