Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor

Biochem Biophys Res Commun. 2005 Jan 28;326(4):744-51. doi: 10.1016/j.bbrc.2004.11.120.


A lysophospholipid series, such as lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylcholine (LPC), is a bioactive lipid mediator with diverse physiological and pathological functions. LPC has been reported to induce insulin secretion from pancreatic beta-cells, however, the precise mechanism has remained elusive to date. Here we show that an orphan G-protein-coupled receptor GPR119 plays a pivotal role in this event. LPC potently enhances insulin secretion in response to high concentrations of glucose in the perfused rat pancreas via stimulation of adenylate cyclase, and dose-dependently induces intracellular cAMP accumulation and insulin secretion in a mouse pancreatic beta-cell line, NIT-1 cells. The Gs-protein-coupled receptor for LPC was identified as GPR119, which is predominantly expressed in the pancreas. GPR119-specific siRNA significantly blocked LPC-induced insulin secretion from NIT-1 cells. Our findings suggest that GPR119, which is a novel endogenous receptor for LPC, is involved in insulin secretion from beta-cells, and is a potential target for anti-diabetic drug development.

MeSH terms

  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Glucose / metabolism*
  • Hormones / metabolism
  • Humans
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • Lysophosphatidylcholines / pharmacology*
  • Male
  • Organ Specificity
  • Pancreas
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / metabolism*
  • Tissue Distribution


  • Hormones
  • Insulin
  • Lysophosphatidylcholines
  • Receptors, G-Protein-Coupled
  • Glucose