title: Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146.
abstract: 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.
authors.affiliation: 1] Division of Endocrinology, Diabetology, Angiology and Nephrology, Department of Internal Medicine 4, University Hospital Tuebingen, Germany [2] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [3] German Center for Diabetes Research (DZD), Tübingen [4].
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.affiliation: 1] CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China [2].
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tuebingen, Sand 14, 72076 Tuebingen, Germany [2].
authors.forename: Erhan
authors.initials: E
authors.lastname: Kenar
authors.affiliation: Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tuebingen, Sand 14, 72076 Tuebingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kohlbacher
authors.affiliation: 1] Division of Endocrinology, Diabetology, Angiology and Nephrology, Department of Internal Medicine 4, University Hospital Tuebingen, Germany [2] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [3] German Center for Diabetes Research (DZD), Tübingen.
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.affiliation: 1] Division of Endocrinology, Diabetology, Angiology and Nephrology, Department of Internal Medicine 4, University Hospital Tuebingen, Germany [2] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [3] German Center for Diabetes Research (DZD), Tübingen.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: 1] Division of Endocrinology, Diabetology, Angiology and Nephrology, Department of Internal Medicine 4, University Hospital Tuebingen, Germany [2] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [3] German Center for Diabetes Research (DZD), Tübingen.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.affiliation: 1] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [2] German Center for Diabetes Research (DZD), Tübingen [3] Division of Clinical Chemistry and Pathobiochemistry, Department of Internal Medicine 4, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005951:Glucose Tolerance Test; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein