Diabetologisk disputation
Abstracts
Generation of Oscillatory Ca2+ Signalling in Pancreatic beta-cells and
Islets of Langerhans by Yi-Jia Liu, 1997, ISBN 91-554-4082-7
Biomedium, Box 571, Faculty of Medicine, 751 23 Uppsala
Mechanisms underlying oscillatory Ca2+ signalling were studied in individual pancreatic beta-cells and intact islets of Langerhans using microfluorometry, digital imaging and confocal techniques. Glucose stimulation of insulin release is mediated by increase of the cytoplasmic Ca2+ conctration(i) of the pancreatic beta-cells. In individual beta-cells the glucose response was characterized by periodic depolarization with influx of Ca2+ through voltage-dependent channels resulting in slow oscillationsof Ca2+(i) transients, which were superimposed on the slow oscillations. The transients were due to depolarization-dependent formation of IP3, which mobilizes intracellular Ca2+by acting on IP3 receptors sensitized by cAMP. Pancreatic islets exposed to 11 mM glucose exhibited complex variations of Ca2+(i) with slow (0.3-0.9 per min) or fast (2-7 per min) oscillations or with a mixed pattern. The slow oscillations are similar to those in individual beta-cells. Although the fast ones also correspond to periodic influx of Ca2+ through voltage-dependent channels, they somehow depend also on mobilization of Ca2+ from intracellular stores. Glucagon promotes the fast pattern by facilatating such mobilization.
It is proposed that Ca2+(i) transients generated in different beta-cells within a coupled islet syncytium provide a hyperpolarizing signal which breaks the slow type of Ca2+(i) oscillations into regular fast ones. The mixed pattern with slow and superimposed fast oscillations can be explained by the simultaneous presence of separate cell populations with the respective responses. Depletion of intracellular Ca2+ triggered a store-operated Ca2+ entry mechanism in individual beta-cells. By promoting intracellular Ca2+ sequestration glucose inhibits this entry. Although Sr2+ accumulates into and is released from the IP3-sensitive stores the store-operated pathway appearsto have a limited permeability for this cation. When Sr2+ and Ca2+ were used to elucidate the role of store-operated entry it was found to be a minor pathway, which becomes much up-regulated during culture of the beta-cells.
