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Wagner, R. ; Hieronimus, A. ; Lamprinou, A. ; Heni, M. ; Hatziagelaki, E.* ; Ullrich, S. ; Stefan, N. ; Staiger, H. ; Häring, H.-U. ; Fritsche, A.

Peroxisome Proliferator-Activated Receptor Gamma (PPARG) modulates Free Fatty Acid Receptor 1 (FFAR1) dependent insulin secretion in humans.

Mol. Metab. 3, 676-680 (2014)
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Genetic variation in FFAR1 modulates insulin secretion dependent on non-esterified fatty acid (NEFA) concentrations. We previously demonstrated lower insulin secretion in minor allele carriers of PPARG Pro12Ala in high-NEFA environment, but the mode of action could not been revealed. We tested if this effect is mediated by FFAR1 in humans. Subjects with increased risk of diabetes who underwent oral glucose tolerance tests were genotyped for 7 tagging SNPs in FFAR1 and PPARG Pro12Ala. The FFAR1 SNPs rs12462800 and rs10422744 demonstrated interactions with PPARG on insulin secretion. FFAR1 rs12462800 (p = 0.0006) and rs10422744 (p = 0.001) were associated with reduced insulin secretion in participants concomitantly carrying the PPARG minor allele and having high fasting FFA. These results suggest that the minor allele of the PPARG SNP exposes its carriers to modulatory effects of FFAR1 on insulin secretion. This subphenotype may define altered responsiveness to FFAR1-agonists, and should be investigated in further studies.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Ffar1 ; Ffar1, Free Fatty Acid Receptor 1 ; Free Fatty Acid Receptor 1 ; G-protein Coupled Receptor 40 ; Gpr40 ; Gpr40, G-protein Coupled Receptor 40 ; Insulin Secretion ; Nefa, Non-esterified Fatty Acids ; Ogtt, Oral Glucose Tolerance Test ; Pparg ; Tuef, Tuebingen Family Study
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 3, Issue: 6, Pages: 676-680 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
G-502400-002
PubMed ID 25161890
DOI 10.1016/j.molmet.2014.07.001
Erfassungsdatum 2014-08-29
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