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Miedzybrodzka EL, Foreman RE, Lu VB, et al. Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids. Mol Metab. 2021;54:101356doi: 10.1016/j.molmet.2021.101356.
Miedzybrodzka, E. L., Foreman, R. E., Lu, V. B., George, A. L., Smith, C. A., Larraufie, P., Kay, R. G., Goldspink, D. A., Reimann, F., & Gribble, F. M. (2021). Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids. Molecular metabolism, 54101356. https://doi.org/10.1016/j.molmet.2021.101356
Miedzybrodzka, Emily L, et al. "Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids." Molecular metabolism vol. 54 (2021): 101356. doi: https://doi.org/10.1016/j.molmet.2021.101356
Miedzybrodzka EL, Foreman RE, Lu VB, George AL, Smith CA, Larraufie P, Kay RG, Goldspink DA, Reimann F, Gribble FM. Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids. Mol Metab. 2021 Oct 15;54:101356. doi: 10.1016/j.molmet.2021.101356. Epub 2021 Oct 15. PMID: 34662713; PMCID: PMC8590067.
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Mol Metab. 2021 Oct 15;54:101356. doi: 10.1016/j.molmet.2021.101356. Epub 2021 Oct 15.

Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids.

Molecular metabolism

Emily L Miedzybrodzka, Rachel E Foreman, Van B Lu, Amy L George, Christopher A Smith, Pierre Larraufie, Richard G Kay, Deborah A Goldspink, Frank Reimann, Fiona M Gribble

Affiliations

  1. Wellcome Trust - MRC Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
  2. Wellcome Trust - MRC Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK. Electronic address: [email protected].
  3. Wellcome Trust - MRC Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK. Electronic address: [email protected].

PMID: 34662713 PMCID: PMC8590067 DOI: 10.1016/j.molmet.2021.101356

Abstract

OBJECTIVE: Motilin is a proximal small intestinal hormone with roles in gastrointestinal motility, gallbladder emptying, and hunger initiation. In vivo motilin release is stimulated by fats, bile, and duodenal acidification but the underlying molecular mechanisms of motilin secretion remain poorly understood. This study aimed to establish the key signaling pathways involved in the regulation of secretion from human motilin-expressing M-cells.

METHODS: Human duodenal organoids were CRISPR-Cas9 modified to express the fluorescent protein Venus or the Ca

RESULTS: Human duodenal M-cells synthesize active forms of motilin and acyl-ghrelin in organoid culture, and also co-express cholecystokinin (CCK). Activation of the bile acid receptor GPBAR1 stimulated a 3.4-fold increase in motilin secretion and increased action potential firing. Agonists of the long-chain fatty acid receptor FFA1 and monoacylglycerol receptor GPR119 stimulated secretion by 2.4-fold and 1.5-fold, respectively. Acidification (pH 5.0) was a potent stimulus of M-cell calcium elevation and electrical activity, an effect attributable to acid-sensing ion channels, and a modest inducer of motilin release.

CONCLUSIONS: This study presents the first in-depth transcriptomic and functional characterization of human duodenal motilin-expressing cells. We identify several receptors important for the postprandial and interdigestive regulation of motilin release.

Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.

Keywords: Enteroendocrine hormones; Human intestinal organoids; Motilin; Secretion

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