Signalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cells
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Pais, R., Gribble, F., & Reimann, F. (2015). Signalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cells. Peptides, 77 9-15. https://doi.org/10.1016/j.peptides.2015.07.019
Glucagon like peptide-1 is an insulinotropic hormone released from intestinal L-cells in response to food ingestion. Here, we investigated mechanisms underlying the sensing of peptones by primary small intestinal L-cells. Meat, casein and vegetable-derived peptones (5mg/ml), the L-amino acids Phe, Trp, Gln and Ala (20 mM each), and the dipeptide glycine-sarcosine (20 mM) stimulated GLP-1 secretion from primary cultures prepared from the small intestine. Further mechanistic studies were performed with meat peptone, and revealed the elevation of intracellular calcium in L-cells. Inhibition of the calcium sensing receptor (CaSR), transient receptor potential (TRP) channels and Q-type voltage gated calcium channels (VGCC) significantly attenuated peptone-stimulated GLP-1 release and reduced intracellular Ca2+ responses. CaSR inhibition also attenuated the GLP-1 secretory response to Gln. Targeting these pathways in L-cells could be used to increase endogenous production of GLP-1 and offer exploitable avenues for the development of therapeutics to treat diabetes and obesity.
This work was funded by grants from the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3) and Full4Health (FP7/2011-2015, grant agreement n° 266408).
External DOI: https://doi.org/10.1016/j.peptides.2015.07.019
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250302
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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