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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
1999-12-7
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pubmed:abstractText |
The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human beta-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25-53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-1349989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-1545870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-7901001,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-7935494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-7935793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8635654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8770920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8799146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8866550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8894494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8923459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8945470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8945471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-8988180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9075818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9199333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9252422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9280302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9326926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9398836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9560151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9588460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9588461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9637677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9648841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9649577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9710595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10545530-9873045
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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 |
0021-9738
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pubmed:author |
pubmed-author:AllenL ILI,
pubmed-author:AyresSS,
pubmed-author:BulmanM PMP,
pubmed-author:ClarkPP,
pubmed-author:DemaineAA,
pubmed-author:DochertyKK,
pubmed-author:EllardSS,
pubmed-author:EvansJ CJC,
pubmed-author:FraylingT MTM,
pubmed-author:HattersleyA TAT,
pubmed-author:MacfarlaneW MWM,
pubmed-author:MillwardAA,
pubmed-author:ShepherdMM,
pubmed-author:WilkinTT
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pubmed:issnType |
Print
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R33-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10545530-Adult,
pubmed-meshheading:10545530-Aged,
pubmed-meshheading:10545530-Blotting, Western,
pubmed-meshheading:10545530-Cell Nucleus,
pubmed-meshheading:10545530-Cells, Cultured,
pubmed-meshheading:10545530-Cytoplasm,
pubmed-meshheading:10545530-DNA Mutational Analysis,
pubmed-meshheading:10545530-Diabetes Mellitus, Type 2,
pubmed-meshheading:10545530-Female,
pubmed-meshheading:10545530-Genetic Predisposition to Disease,
pubmed-meshheading:10545530-Glucose,
pubmed-meshheading:10545530-Homeodomain Proteins,
pubmed-meshheading:10545530-Humans,
pubmed-meshheading:10545530-Insulin,
pubmed-meshheading:10545530-Male,
pubmed-meshheading:10545530-Middle Aged,
pubmed-meshheading:10545530-Mutation, Missense,
pubmed-meshheading:10545530-Pedigree,
pubmed-meshheading:10545530-Phenotype,
pubmed-meshheading:10545530-Phosphorylation,
pubmed-meshheading:10545530-Trans-Activators,
pubmed-meshheading:10545530-Transcription, Genetic
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pubmed:year |
1999
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pubmed:articleTitle |
Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes.
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pubmed:affiliation |
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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