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Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms
Open accessAbstract
Aims/hypothesis Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes and reduced insulin secretion. The transcription factor TCF7L2 is an essential factor for glucagon-like peptide-1 (GLP-1) secretion from intestinal L cells. We studied whether a defect in the enteroinsular axis contributes to impaired insulin secretion in carriers of TCF7L2 polymorphisms.Methods We genotyped 1,110 non-diabetic German participants for five single nucleotide polymorphisms in TCF7L2. All participants underwent an OGTT; GLP-1 secretion was measured in 155 participants. In 210 participants, an IVGTT combined with a hyperinsulinaemic-euglycaemic clamp was performed. In another 160 participants from the Netherlands and 73 from Germany, a hyperglycaemic clamp (10 mmol/l) was performed. In 73 German participants this clamp was combined with a GLP-1 infusion and an arginine bolus.Results The OGTT data confirmed that variants in TCF7L2 are associated with reduced insulin secretion. In contrast, insulin secretion induced by an i.v. glucose challenge in the IVGTT and hyperglycaemic clamp was not different between the genotypes. GLP-1 concentrations during the OGTT were not influenced by the TCF7L2 variants. However, GLP-1-infusion combined with a hyperglycaemic clamp showed a significant reduction in GLP-1-induced insulin secretion in carriers of the risk allele in two variants (rs7903146, rs12255372, p < 0.02).Conclusions/interpretation Variants of TCF7L2 specifically impair GLP-1-induced insulin secretion. This seems to be rather the result of a functional defect in the GLP-1 signalling in beta cells than a reduction in GLP-1 secretion. This defect might explain the impaired insulin secretion in carriers of the risk alleles and confers the increased risk of type 2 diabetes.
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“However, there has been some suggestion that there is interindividual heterogeneity in response to GLP-1, raising the possibility that some individuals may benefit more from such therapy than others earlier in the disease (25, 31).”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [25]
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Cites
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Grant, S. F. A., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., et al. (2006) · Nature Genetics · doi:10.1038/ng1732 · Cited by 2,287
TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program
Florez, J. C., Jablonski, K. A., Bayley, N., Pollin, T. I., de Bakker, P. I. W., Shuldiner, A. R., Knowler, W. C., Nathan, D. M., & Altshuler, D. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062418 · Cited by 834
Deacon, C. F., Johnsen, A. H., & Holst, J. J. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.3.7883856 · Cited by 792
Self-citationHansen, L., Deacon, C. F., Ørskov, C., & Holst, J. J. (1999) · Endocrinology · doi:10.1210/endo.140.11.7143 · Cited by 595
Self-citationRefining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
Helgason, A., Pálsson, S., Þorleifsson, G., Grant, S. F. A., Emilsson, V., Gunnarsdottir, S., Adeyemo, A., Chen, Y., Chen, G., Reynisdóttir, I., et al. (2007) · Nature Genetics · doi:10.1038/ng1960 · Cited by 529
Yi, F., Brubaker, P. L., & Jin, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411487200 · Cited by 417
Scheinfeld, A. (1945) · The American Journal of the Medical Sciences · doi:10.1097/00000441-194507000-00025 · Cited by 381
Saxena, R., Gianniny, L., Burtt, N. P., Lyssenko, V., Giuducci, C., Sjögren, M., Florez, J. C., Almgren, P., Isomaa, B., Orho‐Melander, M., et al. (2006) · Diabetes · doi:10.2337/db06-0381 · Cited by 373
The Peroxisome Proliferator-Activated Receptor-γ2 Pro12Ala Polymorphism
Stümvoll, M., & Häring, H. U. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2341 · Cited by 329
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Metadata
- Authors
- Schäfer, S. A., Tschritter, O., Machicao, F., Thamer, C., Stefan, N., Gallwitz, B., Holst, J. J., Dekker, J. M., t’Hart, L. M., Nijpels, G., van Haeften, T. W., Häring, H. U., & Fritsche, A.
- Affiliations
- University of Tübingen (DE)
- University of Copenhagen (DK)
- Amsterdam Public Health (NL)
- Corresponding author
- Fritsche, A.
- Venue
- Diabetologia
- Published
- 2007-07-28
- Volume
- 50
- Issue
- 12
- Pages
- 2443-2450
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC2063563
- OpenAlex
- W2132717133
- Cited by
- 308
- References
- 30
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 18 · 2018: 14 · 2017: 10 · 2016: 15 · 2015: 15 · 2014: 26 · 2013: 17 · 2012: 23
- FWCI
- 32.85
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 114)
- ZonMw
- Centre for Medical Systems Biology
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- TCF7L2, glucagon-like peptide-1, insulin secretion, type 2 diabetes risk, single nucleotide polymorphisms, enteroinsular axis, GLP-1 secretion, GLP-1 receptor, rs7903146, rs12255372, risk alleles
- MeSH terms
- Insulin Secretion, Adult, Arginine, Blood Glucose, Female, Glucose Tolerance Test, Heterozygote, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Glucose Clamp Technique, Glucose Intolerance, Polymorphism, Single Nucleotide, TCF Transcription Factors, Glucagon-Like Peptide 1, Transcription Factor 7-Like 2 Protein
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