Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors. / Modvig, Ida M.; Kuhre, Rune E.; Holst, Jens Juul.

In: Physiological Reports, Vol. 7, No. 8, e14056, 04.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Modvig, IM, Kuhre, RE & Holst, JJ 2019, 'Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors', Physiological Reports, vol. 7, no. 8, e14056. https://doi.org/10.14814/phy2.14056

APA

Modvig, I. M., Kuhre, R. E., & Holst, J. J. (2019). Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors. Physiological Reports, 7(8), [e14056]. https://doi.org/10.14814/phy2.14056

Vancouver

Modvig IM, Kuhre RE, Holst JJ. Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors. Physiological Reports. 2019 Apr;7(8). e14056. https://doi.org/10.14814/phy2.14056

Author

Modvig, Ida M. ; Kuhre, Rune E. ; Holst, Jens Juul. / Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors. In: Physiological Reports. 2019 ; Vol. 7, No. 8.

Bibtex

@article{12670b4fcb8445dd8f4ecec848ba85d4,
title = "Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors",
abstract = "Protein intake robustly stimulates the secretion of the incretin hormone, glucagon- like peptide-1 (GLP-1) but the molecular mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiologically relevant model-the isolated perfused proximal rat small intestine. Intraluminal protein hydrolysates derived from meat (peptone; 50 mg/mL) increased GLP-1 secretion 2.3-fold (from a basal secretion of 110 +/- 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium-Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone-induced GLP-1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP-1 secretion. Inhibitors of voltage-gated L-type Ca2+ channels had no effect on secretion suggesting that peptone-mediated GLP-1 secretion is not mediated by L-cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP-1.",
keywords = "Amino acid sensing, Calcium-Sensing Receptor, glucagon-like peptide 1, peptide transporter 1, peptone",
author = "Modvig, {Ida M.} and Kuhre, {Rune E.} and Holst, {Jens Juul}",
year = "2019",
month = "4",
doi = "10.14814/phy2.14056",
language = "English",
volume = "7",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "Wiley Periodicals, Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors

AU - Modvig, Ida M.

AU - Kuhre, Rune E.

AU - Holst, Jens Juul

PY - 2019/4

Y1 - 2019/4

N2 - Protein intake robustly stimulates the secretion of the incretin hormone, glucagon- like peptide-1 (GLP-1) but the molecular mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiologically relevant model-the isolated perfused proximal rat small intestine. Intraluminal protein hydrolysates derived from meat (peptone; 50 mg/mL) increased GLP-1 secretion 2.3-fold (from a basal secretion of 110 +/- 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium-Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone-induced GLP-1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP-1 secretion. Inhibitors of voltage-gated L-type Ca2+ channels had no effect on secretion suggesting that peptone-mediated GLP-1 secretion is not mediated by L-cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP-1.

AB - Protein intake robustly stimulates the secretion of the incretin hormone, glucagon- like peptide-1 (GLP-1) but the molecular mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiologically relevant model-the isolated perfused proximal rat small intestine. Intraluminal protein hydrolysates derived from meat (peptone; 50 mg/mL) increased GLP-1 secretion 2.3-fold (from a basal secretion of 110 +/- 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium-Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone-induced GLP-1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP-1 secretion. Inhibitors of voltage-gated L-type Ca2+ channels had no effect on secretion suggesting that peptone-mediated GLP-1 secretion is not mediated by L-cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP-1.

KW - Amino acid sensing

KW - Calcium-Sensing Receptor

KW - glucagon-like peptide 1

KW - peptide transporter 1

KW - peptone

U2 - 10.14814/phy2.14056

DO - 10.14814/phy2.14056

M3 - Journal article

C2 - 31020803

VL - 7

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 8

M1 - e14056

ER -

ID: 223925683