Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans

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Standard

Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans. / Wagner, Robert; Kaiser, Gabriele; Gerst, Felicia; Christiansen, Elisabeth; Due-Hansen, Maria Elisabeth; Grundmann, Manuel; Machicao, Fausto; Peter, Andreas; Kostenis, Evi; Ulven, Trond; Fritsche, Andreas; Häring, Hans-Ulrich; Ullrich, Susanne.

In: Diabetes, Vol. 62, No. 6, 01.02.2013, p. 2106-2111.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wagner, R, Kaiser, G, Gerst, F, Christiansen, E, Due-Hansen, ME, Grundmann, M, Machicao, F, Peter, A, Kostenis, E, Ulven, T, Fritsche, A, Häring, H-U & Ullrich, S 2013, 'Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans', Diabetes, vol. 62, no. 6, pp. 2106-2111. https://doi.org/10.2337/db12-1249

APA

Wagner, R., Kaiser, G., Gerst, F., Christiansen, E., Due-Hansen, M. E., Grundmann, M., Machicao, F., Peter, A., Kostenis, E., Ulven, T., Fritsche, A., Häring, H-U., & Ullrich, S. (2013). Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans. Diabetes, 62(6), 2106-2111. https://doi.org/10.2337/db12-1249

Vancouver

Wagner R, Kaiser G, Gerst F, Christiansen E, Due-Hansen ME, Grundmann M et al. Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans. Diabetes. 2013 Feb 1;62(6):2106-2111. https://doi.org/10.2337/db12-1249

Author

Wagner, Robert ; Kaiser, Gabriele ; Gerst, Felicia ; Christiansen, Elisabeth ; Due-Hansen, Maria Elisabeth ; Grundmann, Manuel ; Machicao, Fausto ; Peter, Andreas ; Kostenis, Evi ; Ulven, Trond ; Fritsche, Andreas ; Häring, Hans-Ulrich ; Ullrich, Susanne. / Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans. In: Diabetes. 2013 ; Vol. 62, No. 6. pp. 2106-2111.

Bibtex

@article{6d943b69e36c45dc8138002e9e085223,
title = "Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans",
abstract = "The role of free fatty acid receptor 1 (FFAR1/GPR40) in glucose homeostasis is still incompletely understood. Small receptor agonists stimulating insulin secretion are under investigation for the treatment of type 2 diabetes. Surprisingly, genome-wide association studies did not discover diabetes risk variants in FFAR1. We reevaluated the role of FFAR1 in insulin secretion using a specific agonist, FFAR1-knockout mice and human islets. Nondiabetic individuals were metabolically phenotyped and genotyped. In vitro experiments indicated that palmitate and a specific FFAR1-agonist, TUG-469, stimulate glucose-induced insulin secretion through FFAR1. The pro-apoptotic effect of chronic exposure of beta-cells to palmitate was independent of FFAR1. TUG-469 was protective, while inhibition of FFAR1 promoted apoptosis. In accordance with the pro-apoptotic effect of palmitate, in vivo crosssectional observations demonstrated a negative association between fasting free fatty acids (NEFA) and insulin secretion. As NEFA stimulate secretion through FFAR1, we examined the interaction of genetic variation in FFAR1 with NEFA and insulin secretion. The inverse association of NEFA and secretion was modulated by rs1573611 and became steeper for carriers of the minor allele. In conclusion, FFAR1 agonists support beta-cell function, but variation in FFAR1 influences NEFA effects on insulin secretion and could, therefore, affect therapeutic efficacy of FFAR1-agonists.",
author = "Robert Wagner and Gabriele Kaiser and Felicia Gerst and Elisabeth Christiansen and Due-Hansen, {Maria Elisabeth} and Manuel Grundmann and Fausto Machicao and Andreas Peter and Evi Kostenis and Trond Ulven and Andreas Fritsche and Hans-Ulrich H{\"a}ring and Susanne Ullrich",
year = "2013",
month = feb,
day = "1",
doi = "10.2337/db12-1249",
language = "English",
volume = "62",
pages = "2106--2111",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

RIS

TY - JOUR

T1 - Reevaluation of Fatty acid receptor 1 (FFAR1/GPR40) as drug target for the stimulation of insulin secretion in humans

AU - Wagner, Robert

AU - Kaiser, Gabriele

AU - Gerst, Felicia

AU - Christiansen, Elisabeth

AU - Due-Hansen, Maria Elisabeth

AU - Grundmann, Manuel

AU - Machicao, Fausto

AU - Peter, Andreas

AU - Kostenis, Evi

AU - Ulven, Trond

AU - Fritsche, Andreas

AU - Häring, Hans-Ulrich

AU - Ullrich, Susanne

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The role of free fatty acid receptor 1 (FFAR1/GPR40) in glucose homeostasis is still incompletely understood. Small receptor agonists stimulating insulin secretion are under investigation for the treatment of type 2 diabetes. Surprisingly, genome-wide association studies did not discover diabetes risk variants in FFAR1. We reevaluated the role of FFAR1 in insulin secretion using a specific agonist, FFAR1-knockout mice and human islets. Nondiabetic individuals were metabolically phenotyped and genotyped. In vitro experiments indicated that palmitate and a specific FFAR1-agonist, TUG-469, stimulate glucose-induced insulin secretion through FFAR1. The pro-apoptotic effect of chronic exposure of beta-cells to palmitate was independent of FFAR1. TUG-469 was protective, while inhibition of FFAR1 promoted apoptosis. In accordance with the pro-apoptotic effect of palmitate, in vivo crosssectional observations demonstrated a negative association between fasting free fatty acids (NEFA) and insulin secretion. As NEFA stimulate secretion through FFAR1, we examined the interaction of genetic variation in FFAR1 with NEFA and insulin secretion. The inverse association of NEFA and secretion was modulated by rs1573611 and became steeper for carriers of the minor allele. In conclusion, FFAR1 agonists support beta-cell function, but variation in FFAR1 influences NEFA effects on insulin secretion and could, therefore, affect therapeutic efficacy of FFAR1-agonists.

AB - The role of free fatty acid receptor 1 (FFAR1/GPR40) in glucose homeostasis is still incompletely understood. Small receptor agonists stimulating insulin secretion are under investigation for the treatment of type 2 diabetes. Surprisingly, genome-wide association studies did not discover diabetes risk variants in FFAR1. We reevaluated the role of FFAR1 in insulin secretion using a specific agonist, FFAR1-knockout mice and human islets. Nondiabetic individuals were metabolically phenotyped and genotyped. In vitro experiments indicated that palmitate and a specific FFAR1-agonist, TUG-469, stimulate glucose-induced insulin secretion through FFAR1. The pro-apoptotic effect of chronic exposure of beta-cells to palmitate was independent of FFAR1. TUG-469 was protective, while inhibition of FFAR1 promoted apoptosis. In accordance with the pro-apoptotic effect of palmitate, in vivo crosssectional observations demonstrated a negative association between fasting free fatty acids (NEFA) and insulin secretion. As NEFA stimulate secretion through FFAR1, we examined the interaction of genetic variation in FFAR1 with NEFA and insulin secretion. The inverse association of NEFA and secretion was modulated by rs1573611 and became steeper for carriers of the minor allele. In conclusion, FFAR1 agonists support beta-cell function, but variation in FFAR1 influences NEFA effects on insulin secretion and could, therefore, affect therapeutic efficacy of FFAR1-agonists.

U2 - 10.2337/db12-1249

DO - 10.2337/db12-1249

M3 - Journal article

VL - 62

SP - 2106

EP - 2111

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

ID: 189158148