Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells

J Physiol. 2011 Mar 1;589(Pt 5):1081-93. doi: 10.1113/jphysiol.2010.198069. Epub 2011 Jan 4.


Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Electric Stimulation*
  • Electrophysiology
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Glucagon-Like Peptide 1 / metabolism*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Mice
  • Mice, Transgenic
  • Nifedipine / pharmacology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction


  • Calcium Channel Blockers
  • Calcium Channels
  • Glucagon-Like Peptide 1
  • Nifedipine
  • Calcium