Mechanisms of coordination of Ca2+ signals in pancreatic islet cells.
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.
Bertuzzi
F
F
Surgical Department, and Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, S. Raffaele Scientific Institute, Milan, Italy. bertuzzi.federico@hsr.it
Davalli
A M
AM
Nano
R
R
Socci
C
C
Codazzi
F
F
Fesce
R
R
Di Carlo
V
V
Pozza
G
G
Grohovaz
F
F
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
C119129:18alpha-glycyrrhetinic acid; D005947:Glucose; D006034:Glycyrrhetinic Acid; D002118:Calcium