Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells

J Biol Chem. 2017 Jun 30;292(26):10855-10864. doi: 10.1074/jbc.M117.788653. Epub 2017 May 22.


The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon-like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+] i ) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells. The [Ca2+] i increase was suppressed by an antagonist for G protein-coupled receptor 55 (GPR55) and by silencing of GPR55 expression, indicating involvement of Gq and G12/13 signaling pathways in the LPI-induced increased [Ca2+] i levels and GLP-1 secretion. However, GPR55 agonists did not mimic many of the effects of LPI. We also found that phospholipase C inhibitor and Rho-associated kinase inhibitor suppressed the [Ca2+] i increase and that LPI increased the number of focal adhesions, indicating actin reorganization. Of note, blockage or silencing of transient receptor potential cation channel subfamily V member 2 (TRPV2) channels suppressed both the LPI-induced [Ca2+] i increase and GLP-1 secretion. Furthermore, LPI accelerated TRPV2 translocation to the plasma membrane, which was significantly suppressed by a GPR55 antagonist. These findings suggest that TRPV2 activation via actin reorganization induced by Gq and G12/13 signaling is involved in LPI-stimulated GLP-1 secretion in enteroendocrine L cells. Because GPR55 agonists largely failed to mimic the effects of LPI, its actions on L cells are at least partially independent of GPR55 activation.

Keywords: G protein-coupled receptor (GPCR); cell signaling; exocytosis; hormone; imaging; transient receptor potential channels (TRP channels).

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Enteroendocrine Cells / metabolism*
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits / metabolism
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism*
  • Lysophospholipids / metabolism*
  • Mice
  • Protein Transport / physiology
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • Calcium Channels
  • GPR55 protein, mouse
  • GTP-Binding Protein alpha Subunits
  • Lysophospholipids
  • Receptors, Cannabinoid
  • TRPV Cation Channels
  • Trpv2 protein, mouse
  • lysophosphatidylinositol
  • Glucagon-Like Peptide 1