title: Signalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cells.
abstract: 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 (5 mg/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 Ca(2+) 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.
authors.affiliation: Wellcome Trust - MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.affiliation: Wellcome Trust - MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: fmg23@cam.ac.uk.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.affiliation: Wellcome Trust - MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: fr222@cam.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D008822:Mice, Transgenic; D010461:Peptones / Q000494:pharmacology / Q000502:physiology*; D046509:Tissue Culture Techniques; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D010461:Peptones; D050051:Transient Receptor Potential Channels; D052216:Glucagon-Like Peptide 1
keywords: Enteroendocrine; GLP-1; L-cell; Peptones