title: Plasma Membrane Phosphatidylinositol 4,5-Bisphosphate Regulates Ca(2+)-Influx and Insulin Secretion from Pancreatic β Cells.
abstract: Insulin secretion from pancreatic β cells is regulated by the blood glucose concentration and occurs through Ca(2+)-triggered exocytosis. The activities of multiple ion channels in the β cell plasma membrane are required to fine-tune insulin secretion in order to maintain normoglycemia. Phosphoinositide lipids in the plasma membrane often gate ion channels, and variations in the concentration of these lipids affect ion-channel open probability and conductance. Using light-regulated synthesis or depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2), we found that this lipid positively regulated both depolarization- and glucose-triggered Ca(2+) influx in a dose-dependent manner. Small reductions of PI(4,5)P2 caused by brief illumination resulted in partial suppression of Ca(2+) influx that followed the kinetics of the lipid, whereas depletion resulted in marked inhibition of both Ca(2+) influx and insulin secretion.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden.
authors.forename: Beichen
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden.
authors.forename: Phuoc My
authors.initials: PM
authors.lastname: Nguyen
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden.
authors.forename: Alenka
authors.initials: A
authors.lastname: Guček
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden.
authors.forename: Antje
authors.initials: A
authors.lastname: Thonig
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Barg
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Husargatan 3, Box 571, 75123 Uppsala, Sweden. Electronic address: olof.idevall@mcb.uu.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Idevall-Hagren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*
chemical_list: D007328:Insulin; D019269:Phosphatidylinositol 4,5-Diphosphate; D002118:Calcium