Cholesterol regulates glucose-stimulated insulin secretion through phosphatidylinositol 4,5-bisphosphate Academic Article uri icon


MeSH Major

  • Cholesterol
  • Glucose
  • Insulin
  • Insulin-Secreting Cells
  • Models, Biological
  • Phosphatidylinositol 4,5-Diphosphate


  • Membrane cholesterol modulates the ability of glucose to stimulate insulin secretion from pancreatic beta-cells. The molecular mechanism by which this occurs is not understood. Here, we show that in cultured beta-cells, cholesterol acts through phosphatidylinositol 4,5-bisphosphate (PIP(2)) to regulate actin dynamics, plasma membrane potential, and glucose-stimulated insulin secretion. Cholesterol-overloaded beta-cells exhibited decreased PIP(2) hydrolysis, with diminished glucose-induced actin reorganization, membrane depolarization, and insulin secretion. The converse findings were observed in cholesterol-depleted cells. These results support a model in which cholesterol depletion is coupled through PIP(2) to enhance both plasma membrane Ca2+ influx from the extracellular space, as well as inositol 1,4,5-triphosphate-stimulated Ca2+ efflux from intracellular stores. The inability to increase cytosolic Ca2+ may be the main underlying factor to account for impaired glucose-stimulated insulin secretion in cholesterol-overloaded beta-cells.

publication date

  • October 23, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2785582

Digital Object Identifier (DOI)

  • 10.1074/jbc.M109.038034

PubMed ID

  • 19729450

Additional Document Info

start page

  • 29489

end page

  • 98


  • 284


  • 43