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Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146
An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055885/ https://www.ncbi.nlm.nih.gov/pubmed/24925104 http://dx.doi.org/10.1038/srep05296 |
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author | Wagner, Robert Li, Jia Kenar, Erhan Kohlbacher, Oliver Machicao, Fausto Häring, Hans-Ulrich Fritsche, Andreas Xu, Guowang Lehmann, Rainer |
author_facet | Wagner, Robert Li, Jia Kenar, Erhan Kohlbacher, Oliver Machicao, Fausto Häring, Hans-Ulrich Fritsche, Andreas Xu, Guowang Lehmann, Rainer |
author_sort | Wagner, Robert |
collection | PubMed |
description | An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion. |
format | Online Article Text |
id | pubmed-4055885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40558852014-06-16 Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 Wagner, Robert Li, Jia Kenar, Erhan Kohlbacher, Oliver Machicao, Fausto Häring, Hans-Ulrich Fritsche, Andreas Xu, Guowang Lehmann, Rainer Sci Rep Article An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion. Nature Publishing Group 2014-06-13 /pmc/articles/PMC4055885/ /pubmed/24925104 http://dx.doi.org/10.1038/srep05296 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Wagner, Robert Li, Jia Kenar, Erhan Kohlbacher, Oliver Machicao, Fausto Häring, Hans-Ulrich Fritsche, Andreas Xu, Guowang Lehmann, Rainer Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title | Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title_full | Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title_fullStr | Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title_full_unstemmed | Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title_short | Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146 |
title_sort | clinical and non-targeted metabolomic profiling of homozygous carriers of transcription factor 7-like 2 variant rs7903146 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055885/ https://www.ncbi.nlm.nih.gov/pubmed/24925104 http://dx.doi.org/10.1038/srep05296 |
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