Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors.
Physiol Rep
; 7(8): e14056, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-31020803
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.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptonas
/
Receptores de Detecção de Cálcio
/
Peptídeo 1 Semelhante ao Glucagon
/
Absorção Intestinal
Limite:
Animals
Idioma:
En
Revista:
Physiol Rep
Ano de publicação:
2019
Tipo de documento:
Article