Signalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cells

Publication date: Available online 26 July 2015 Source:Peptides Author(s): Ramona Pais, Fiona M Gribble, Frank Reimann 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 (20mM each), and the dipeptide glycine-sarcosine (20mM) 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.
Source: Peptides - Category: Biochemistry Source Type: research