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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 3, Heft: 6, Seiten: 676-680 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) 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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