GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

Biochem Biophys Res Commun. 2015 Dec;468(1-2):306-11. doi: 10.1016/j.bbrc.2015.10.107. Epub 2015 Oct 23.

Abstract

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells.

Keywords: 1,10-Phenanthroline; Bitter taste receptor; Enteroendocrine cell; T2R5; Taste receptor type 2 member 5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Enteroendocrine Cells / drug effects*
  • Enteroendocrine Cells / metabolism
  • Glucagon-Like Peptide 1 / analysis
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Ileum / drug effects
  • Ileum / metabolism
  • Phenanthrolines / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / analysis
  • Receptors, G-Protein-Coupled / metabolism*
  • Taste Receptors, Type 2

Substances

  • Phenanthrolines
  • Receptors, G-Protein-Coupled
  • Taste Receptors, Type 2
  • Glucagon-Like Peptide 1
  • 1,10-phenanthroline