The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line

J Physiol. 2005 Dec 15;569(Pt 3):761-72. doi: 10.1113/jphysiol.2005.098962. Epub 2005 Oct 13.


The incretin hormone, glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells following food ingestion. Its secretion is triggered by a range of nutrients, including fats, carbohydrates and proteins. We reported previously that Na(+)-dependent glutamine uptake triggered electrical activity and GLP-1 release from the L-cell model line GLUTag. However, whereas alanine also triggered membrane depolarization and GLP-1 secretion, the response was Na+ independent. A range of alanine analogues, including d-alanine, beta-alanine, glycine and l-serine, but not d-serine, triggered similar depolarizing currents and elevation of intracellular [Ca2+], a sensitivity profile suggesting the involvement of glycine receptors. In support of this idea, glycine-induced currents and GLP-1 release were blocked by strychnine, and currents showed a 58.5 mV shift in reversal potential per 10-fold change in [Cl-], consistent with the activation of a Cl(-)-selective current. GABA, an agonist of related Cl- channels, also triggered Cl- currents and secretion, which were sensitive to picrotoxin. GABA-triggered [Ca2+]i increments were abolished by bicuculline and partially impaired by (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA), suggesting the involvement of both GABA(A) and GABA(C) receptors. Expression of GABA(A), GABA(C) and glycine receptor subunits was confirmed by RT-PCR. Glycine-triggered GLP-1 secretion was impaired by bumetanide but not bendrofluazide, suggesting that a high intracellular [Cl-] maintained by Na(+)-K(+)-2Cl- cotransporters is necessary for the depolarizing response to glycine receptor ligands. Our results suggest that GABA and glycine stimulate electrical activity and GLP-1 release from GLUTag cells by ligand-gated ion channel activation, a mechanism that might be important in responses to endogenous ligands from the enteric nervous system or dietary sources.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium / metabolism
  • Cell Line, Tumor
  • Chlorides / metabolism
  • Dose-Response Relationship, Drug
  • GABA Antagonists / pharmacology
  • Glucagon-Like Peptide 1 / metabolism*
  • Glycine / pharmacology*
  • Ion Channel Gating / drug effects
  • Mice
  • Neurotransmitter Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, GABA / drug effects
  • Receptors, GABA / genetics
  • Receptors, GABA / metabolism
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Receptors, Glycine / drug effects
  • Receptors, Glycine / genetics
  • Receptors, Glycine / metabolism
  • Sodium Potassium Chloride Symporter Inhibitors / pharmacology
  • Sodium-Potassium-Chloride Symporters / drug effects
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Strychnine / pharmacology
  • gamma-Aminobutyric Acid / pharmacology*


  • Chlorides
  • GABA Antagonists
  • GABA-C receptor
  • Neurotransmitter Agents
  • RNA, Messenger
  • Receptors, GABA
  • Receptors, GABA-A
  • Receptors, Glycine
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sodium-Potassium-Chloride Symporters
  • gamma-Aminobutyric Acid
  • Glucagon-Like Peptide 1
  • Strychnine
  • Calcium
  • Glycine