Gq and Gs signaling acting in synergy to control GLP-1 secretion

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Gq and Gs signaling acting in synergy to control GLP-1 secretion. / Pedersen, Maria Hauge; Ekberg, Jeppe Hvidtfeldt; Engelstoft, Maja Storm; Timshel, Pascal; Madsen, Andreas N; Schwartz, Thue W.

In: Molecular and Cellular Endocrinology, Vol. 449, 07.2017, p. 64-73.

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

Harvard

Pedersen, MH, Ekberg, JH, Engelstoft, MS, Timshel, P, Madsen, AN & Schwartz, TW 2017, 'Gq and Gs signaling acting in synergy to control GLP-1 secretion', Molecular and Cellular Endocrinology, vol. 449, pp. 64-73. https://doi.org/10.1016/j.mce.2016.11.024

APA

Pedersen, M. H., Ekberg, J. H., Engelstoft, M. S., Timshel, P., Madsen, A. N., & Schwartz, T. W. (2017). Gq and Gs signaling acting in synergy to control GLP-1 secretion. Molecular and Cellular Endocrinology, 449, 64-73. https://doi.org/10.1016/j.mce.2016.11.024

Vancouver

Pedersen MH, Ekberg JH, Engelstoft MS, Timshel P, Madsen AN, Schwartz TW. Gq and Gs signaling acting in synergy to control GLP-1 secretion. Molecular and Cellular Endocrinology. 2017 Jul;449:64-73. https://doi.org/10.1016/j.mce.2016.11.024

Author

Pedersen, Maria Hauge ; Ekberg, Jeppe Hvidtfeldt ; Engelstoft, Maja Storm ; Timshel, Pascal ; Madsen, Andreas N ; Schwartz, Thue W. / Gq and Gs signaling acting in synergy to control GLP-1 secretion. In: Molecular and Cellular Endocrinology. 2017 ; Vol. 449. pp. 64-73.

Bibtex

@article{cb27b5d0d3b943e5a00df7abc82adf37,
title = "Gq and Gs signaling acting in synergy to control GLP-1 secretion",
abstract = "GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e.g. GPR119 and TGR5 provide more than additive GLP-1 secretion both ex vivo and in vivo in mice. It is concluded that under physiological circumstances triglyceride metabolites, i.e. long chain fatty acids and 2-monoacyl glycerol plus bile acids, act synergistically through their respective receptors, GPR40, GPR119 and TGR5 to stimulate GLP-1 secretion robustly by combining Gq and Gs signaling pathways.",
author = "Pedersen, {Maria Hauge} and Ekberg, {Jeppe Hvidtfeldt} and Engelstoft, {Maja Storm} and Pascal Timshel and Madsen, {Andreas N} and Schwartz, {Thue W}",
note = "Copyright {\textcopyright} 2016 Elsevier Ireland Ltd. All rights reserved.",
year = "2017",
month = jul,
doi = "10.1016/j.mce.2016.11.024",
language = "English",
volume = "449",
pages = "64--73",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Gq and Gs signaling acting in synergy to control GLP-1 secretion

AU - Pedersen, Maria Hauge

AU - Ekberg, Jeppe Hvidtfeldt

AU - Engelstoft, Maja Storm

AU - Timshel, Pascal

AU - Madsen, Andreas N

AU - Schwartz, Thue W

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2017/7

Y1 - 2017/7

N2 - GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e.g. GPR119 and TGR5 provide more than additive GLP-1 secretion both ex vivo and in vivo in mice. It is concluded that under physiological circumstances triglyceride metabolites, i.e. long chain fatty acids and 2-monoacyl glycerol plus bile acids, act synergistically through their respective receptors, GPR40, GPR119 and TGR5 to stimulate GLP-1 secretion robustly by combining Gq and Gs signaling pathways.

AB - GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e.g. GPR119 and TGR5 provide more than additive GLP-1 secretion both ex vivo and in vivo in mice. It is concluded that under physiological circumstances triglyceride metabolites, i.e. long chain fatty acids and 2-monoacyl glycerol plus bile acids, act synergistically through their respective receptors, GPR40, GPR119 and TGR5 to stimulate GLP-1 secretion robustly by combining Gq and Gs signaling pathways.

U2 - 10.1016/j.mce.2016.11.024

DO - 10.1016/j.mce.2016.11.024

M3 - Journal article

C2 - 27908836

VL - 449

SP - 64

EP - 73

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -

ID: 172434082