Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms. / Modvig, Ida Marie; Kuhre, Rune Ehrenreich; Jepsen, Sara L; Xu, Stella; Engelstoft, Maja S; Egerod, Kristoffer Lihme; Schwartz, Thue W; Ørskov, Cathrine; Rosenkilde, Mette M; Holst, Jens J.

I: American Journal of Physiology: Endocrinology and Metabolism, Bind 320, 2021, s. E874-E885.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Modvig, IM, Kuhre, RE, Jepsen, SL, Xu, S, Engelstoft, MS, Egerod, KL, Schwartz, TW, Ørskov, C, Rosenkilde, MM & Holst, JJ 2021, 'Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms', American Journal of Physiology: Endocrinology and Metabolism, bind 320, s. E874-E885. https://doi.org/10.1152/ajpendo.00026.2021

APA

Modvig, I. M., Kuhre, R. E., Jepsen, S. L., Xu, S., Engelstoft, M. S., Egerod, K. L., Schwartz, T. W., Ørskov, C., Rosenkilde, M. M., & Holst, J. J. (2021). Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms. American Journal of Physiology: Endocrinology and Metabolism, 320, E874-E885. https://doi.org/10.1152/ajpendo.00026.2021

Vancouver

Modvig IM, Kuhre RE, Jepsen SL, Xu S, Engelstoft MS, Egerod KL o.a. Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms. American Journal of Physiology: Endocrinology and Metabolism. 2021;320:E874-E885. https://doi.org/10.1152/ajpendo.00026.2021

Author

Modvig, Ida Marie ; Kuhre, Rune Ehrenreich ; Jepsen, Sara L ; Xu, Stella ; Engelstoft, Maja S ; Egerod, Kristoffer Lihme ; Schwartz, Thue W ; Ørskov, Cathrine ; Rosenkilde, Mette M ; Holst, Jens J. / Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms. I: American Journal of Physiology: Endocrinology and Metabolism. 2021 ; Bind 320. s. E874-E885.

Bibtex

@article{81574877e3394697a366a6ce69ef3148,
title = "Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms",
abstract = "The aim of this study was to explore individual amino acid-stimulated GLP-1 responses and the underlying stimulatory mechanisms, as well as to identify the amino acid-sensing-receptors involved in amino acid-stimulated GLP-1 release. Experiments were primarily based on isolated perfused rat small intestines, which have intact epithelial polarization allowing discrimination between luminal and basolateral mechanisms as well as quantitative studies of intestinal absorption and hormone secretion. Expression analysis of amino acid sensors on isolated murine GLP-1 secreting L-cells was assessed by qPCR. We found that L-valine powerfully stimulated GLP-1 secretion but only from the luminal side (2.9-fold increase). When administered from the vascular side, L-arginine and the aromatic amino acids stimulated GLP-1 secretion equally (2.6-2.9 fold increases). Expression analysis revealed that Casr expression was enriched in murine GLP-1 secreting L-cells, whereas Gpr35, Gprc6a, Gpr142, Gpr93 (Lpar5) and the umami taste receptor subunits Tas1r3 and Tas1r1 were not. Consistently, activation of GPR35, GPR93, GPR142 and the umami taste receptor with specific agonists or allosteric modulators did not increase GLP-1 secretion (P>0.05 for all experiments), whereas vascular inhibition of CaSR reduced GLP-1 secretion in response to luminal infusion of mixed amino acids. In conclusion, amino acids differ in their capacity to stimulate GLP-1 secretion. Some amino acids stimulated secretion only from the intestinal lumen, while other amino acids exclusively stimulated secretion from the vascular side, indicating that amino acid-stimulated GLP-1 secretion involves both apical and basolateral (post-absorptive) sensing mechanisms. Sensing of absorbed amino acids involves CaSR activation as vascular inhibition of CaSR markedly diminished amino acid stimulated GLP-1 release.",
author = "Modvig, {Ida Marie} and Kuhre, {Rune Ehrenreich} and Jepsen, {Sara L} and Stella Xu and Engelstoft, {Maja S} and Egerod, {Kristoffer Lihme} and Schwartz, {Thue W} and Cathrine {\O}rskov and Rosenkilde, {Mette M} and Holst, {Jens J}",
year = "2021",
doi = "10.1152/ajpendo.00026.2021",
language = "English",
volume = "320",
pages = "E874--E885",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",

}

RIS

TY - JOUR

T1 - Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms

AU - Modvig, Ida Marie

AU - Kuhre, Rune Ehrenreich

AU - Jepsen, Sara L

AU - Xu, Stella

AU - Engelstoft, Maja S

AU - Egerod, Kristoffer Lihme

AU - Schwartz, Thue W

AU - Ørskov, Cathrine

AU - Rosenkilde, Mette M

AU - Holst, Jens J

PY - 2021

Y1 - 2021

N2 - The aim of this study was to explore individual amino acid-stimulated GLP-1 responses and the underlying stimulatory mechanisms, as well as to identify the amino acid-sensing-receptors involved in amino acid-stimulated GLP-1 release. Experiments were primarily based on isolated perfused rat small intestines, which have intact epithelial polarization allowing discrimination between luminal and basolateral mechanisms as well as quantitative studies of intestinal absorption and hormone secretion. Expression analysis of amino acid sensors on isolated murine GLP-1 secreting L-cells was assessed by qPCR. We found that L-valine powerfully stimulated GLP-1 secretion but only from the luminal side (2.9-fold increase). When administered from the vascular side, L-arginine and the aromatic amino acids stimulated GLP-1 secretion equally (2.6-2.9 fold increases). Expression analysis revealed that Casr expression was enriched in murine GLP-1 secreting L-cells, whereas Gpr35, Gprc6a, Gpr142, Gpr93 (Lpar5) and the umami taste receptor subunits Tas1r3 and Tas1r1 were not. Consistently, activation of GPR35, GPR93, GPR142 and the umami taste receptor with specific agonists or allosteric modulators did not increase GLP-1 secretion (P>0.05 for all experiments), whereas vascular inhibition of CaSR reduced GLP-1 secretion in response to luminal infusion of mixed amino acids. In conclusion, amino acids differ in their capacity to stimulate GLP-1 secretion. Some amino acids stimulated secretion only from the intestinal lumen, while other amino acids exclusively stimulated secretion from the vascular side, indicating that amino acid-stimulated GLP-1 secretion involves both apical and basolateral (post-absorptive) sensing mechanisms. Sensing of absorbed amino acids involves CaSR activation as vascular inhibition of CaSR markedly diminished amino acid stimulated GLP-1 release.

AB - The aim of this study was to explore individual amino acid-stimulated GLP-1 responses and the underlying stimulatory mechanisms, as well as to identify the amino acid-sensing-receptors involved in amino acid-stimulated GLP-1 release. Experiments were primarily based on isolated perfused rat small intestines, which have intact epithelial polarization allowing discrimination between luminal and basolateral mechanisms as well as quantitative studies of intestinal absorption and hormone secretion. Expression analysis of amino acid sensors on isolated murine GLP-1 secreting L-cells was assessed by qPCR. We found that L-valine powerfully stimulated GLP-1 secretion but only from the luminal side (2.9-fold increase). When administered from the vascular side, L-arginine and the aromatic amino acids stimulated GLP-1 secretion equally (2.6-2.9 fold increases). Expression analysis revealed that Casr expression was enriched in murine GLP-1 secreting L-cells, whereas Gpr35, Gprc6a, Gpr142, Gpr93 (Lpar5) and the umami taste receptor subunits Tas1r3 and Tas1r1 were not. Consistently, activation of GPR35, GPR93, GPR142 and the umami taste receptor with specific agonists or allosteric modulators did not increase GLP-1 secretion (P>0.05 for all experiments), whereas vascular inhibition of CaSR reduced GLP-1 secretion in response to luminal infusion of mixed amino acids. In conclusion, amino acids differ in their capacity to stimulate GLP-1 secretion. Some amino acids stimulated secretion only from the intestinal lumen, while other amino acids exclusively stimulated secretion from the vascular side, indicating that amino acid-stimulated GLP-1 secretion involves both apical and basolateral (post-absorptive) sensing mechanisms. Sensing of absorbed amino acids involves CaSR activation as vascular inhibition of CaSR markedly diminished amino acid stimulated GLP-1 release.

U2 - 10.1152/ajpendo.00026.2021

DO - 10.1152/ajpendo.00026.2021

M3 - Journal article

C2 - 33645250

VL - 320

SP - E874-E885

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

ER -

ID: 258267940