The downregulation of sweet taste receptor signaling in enteroendocrine L-cells mediates 3-deoxyglucosone-induced attenuation of high glucose-stimulated GLP-1 secretion

Arch Physiol Biochem. 2018 Dec;124(5):430-435. doi: 10.1080/13813455.2017.1419366. Epub 2017 Dec 26.

Abstract

Context: Sweet taste receptors (STRs) involve in regulating the release of glucose-stimulated glucagon-like peptide-1 (GLP-1). Our in vivo and in vitro studies found that 3-deoxyglucosone (3DG) inhibited glucose-stimulated GLP-1 secretion.

Objective: This study investigated the role of STRs in 3DG-induced inhibition of high glucose-stimulated GLP-1 secretion.

Methods: STC-1 cells were incubated with lactisole or 3DG for 1 h under 25 mM glucose conditions. Western blotting was used to study the expression of STRs signaling molecules and ELISA was used to analyse GLP-1 and cyclic adenosine monophosphate (cAMP) levels.

Results: Lactisole inhibited GLP-1 secretion. Exposure to 25 mM glucose increased the expressions of STRs subunits when compared with 5.6 mM glucose. 3DG decreased GLP-1 secretion and STRs subunits expressions, with affecting other components of STRs pathway, including the downregulation of transient receptor potential cation channel subfamily M member 5 (TRPM5) expression and the reduction of intracellular cAMP levels.

Conclusion: 3DG attenuates high glucose-stimulated GLP-1 secretion by reducing STR subunit expression and downstream signaling components.

Keywords: 1,2-Dicarbonyl compound; STC-1 cells; TAS1R2; TAS1R3; glucose-stimulated glucagon-like peptide-1 secretion.

MeSH terms

  • Animals
  • Benzene Derivatives / pharmacology
  • Blotting, Western
  • Cell Line
  • Cyclic AMP / metabolism
  • Deoxyglucose / analogs & derivatives*
  • Deoxyglucose / metabolism
  • Dietary Sugars / metabolism
  • Down-Regulation* / drug effects
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide 1 / antagonists & inhibitors
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / metabolism*
  • Intestinal Secretions / drug effects
  • Intestinal Secretions / metabolism
  • Mice
  • Osmolar Concentration
  • Protein Subunits / agonists
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, G-Protein-Coupled / metabolism
  • Second Messenger Systems* / drug effects
  • TRPM Cation Channels / agonists
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / metabolism

Substances

  • Benzene Derivatives
  • Dietary Sugars
  • Protein Subunits
  • Receptors, G-Protein-Coupled
  • TRPM Cation Channels
  • Trpm5 protein, mouse
  • taste receptors, type 1
  • Glucagon-Like Peptide 1
  • Deoxyglucose
  • Cyclic AMP
  • 3-deoxyglucosone
  • Glucose
  • lactisole