Peroxisome proliferator-activated receptor gamma (PPARG) modulates free fatty acid receptor 1 (FFAR1) dependent insulin secretion in humans

被引：10

作者：

Wagner, Robert ^{[1
,2
,3
]}

Hieronimus, Anja ^{[1
,2
,3
]}

Lamprinou, Apostolia ^{[1
,2
,3
]}

Heni, Martin ^{[1
,2
,3
]}

Hatziagelaki, Erifili ^{[4
,5
]}

Ullrich, Susanne ^{[1
,2
,3
]}

Stefan, Norbert ^{[1
,2
,3
]}

Staiger, Harald ^{[1
,2
,3
]}

Haering, Hans-Ulrich ^{[1
,2
,3
]}

Fritsche, Andreas ^{[1
,2
,3
]}

机构：

[1] Univ Tubingen, Univ Hosp, Dept Internal Med, Div Endocrinol Diabetol Nephrol,Vasc Dis & Clin C, Tubingen, Germany

[2] Univ Tubingen IDM, lnst Diabet Res & Metab Dis, Helmholtz Ctr Munich, Tubingen, Germany

[3] German Ctr Diabet Res DZD, Neuherberg, Germany

[4] Univ Athens, Sch Med, Attikon Univ Hosp, Dept Internal Med 2,Res Inst, Athens, Greece

[5] Univ Athens, Sch Med, Attikon Univ Hosp, Ctr Diabet, Athens, Greece

来源：

MOLECULAR METABOLISM | 2014年 / 3卷 / 06期

关键词：

FFAR1; Free fatty acid receptor 1; G-protein coupled receptor 40; GPR40; PPARG; Insulin secretion;

D O I：

10.1016/j.molmet.2014.07.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2014 The Authors. Published by Elsevier GmbH.

引用

页码：676 / 680

页数：5

共 26 条

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