title: Mechanisms of coordination of Ca2+ signals in pancreatic islet cells.
abstract: Within pancreatic islet cells, rhythmic changes in the cytosolic Ca2+ concentration have been reported to occur in response to stimulatory glucose concentrations and to be synchronous with pulsatile release of insulin. We explored the possible mechanisms responsible for Ca2+ signal propagation within islet cells, with particular regard to gap junction communication, the pathway widely credited with being responsible for coordination of the secretory activity. Using fura-2 imaging, we found that multiple mechanisms control Ca2+ signaling in pancreatic islet cells. Gap junction blockade by 18 alpha-glycyrrhetinic acid greatly restricted the propagation of Ca2+ waves induced by mechanical stimulation of cells but affected neither Ca2+ signals nor insulin secretion elicited by glucose elevation. The source of Ca2+ elevation was also different under the two experimental conditions, the first being sustained by release from inner stores and the second by nifedipine-sensitive Ca2+ influx. Furthermore, glucose-induced Ca2+ waves were able to propagate across cell-free clefts, indicating that diffusible factors can control Ca2+ signal coordination. Our results provide evidence that multiple mechanisms of Ca2+ signaling operate in beta-cells and that gap junctions are not required for intercellular Ca2+ wave propagation or insulin secretion in response to glucose.
authors.affiliation: Surgical Department, and Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, S. Raffaele Scientific Institute, Milan, Italy. bertuzzi.federico@hsr.it
authors.forename: F
authors.initials: F
authors.lastname: Bertuzzi
authors.forename: A M
authors.initials: AM
authors.lastname: Davalli
authors.forename: R
authors.initials: R
authors.lastname: Nano
authors.forename: C
authors.initials: C
authors.lastname: Socci
authors.forename: F
authors.initials: F
authors.lastname: Codazzi
authors.forename: R
authors.initials: R
authors.lastname: Fesce
authors.forename: V
authors.initials: V
authors.lastname: Di Carlo
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: F
authors.initials: F
authors.lastname: Grohovaz
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C119129:18alpha-glycyrrhetinic acid; D005947:Glucose; D006034:Glycyrrhetinic Acid; D002118:Calcium