Intra- and inter-cellular signalling in cell societies in endocrine and exocrine pancreas

The spatial and temporal dynamics of periodical [Ca2+](c) increase has prec isely been analyzed by a confocal UV-laser scanning microscopy in islets an d acini isolated from the mouse pancreas. In B cells forming an islet, insu lin secretion is controlled by a variety of secretagogues, and intracellula r signalling processes are diversified in individual secretagogues. The maj or 'initiator' of insulin secretion is exerted by a feedback effect of plas ma glucose directly on the B cells: glucose transported by facilitated diff usion across the B cell membrane is metabolized, ATP thus generated closes ATP-sensitive K+ channels, depolarizes the cell membrane, and then opens vo ltage-sensitive Ca2+ channels. The glucose-activated processes result in pe riodical [Ca2+](c) increases, which synchronize with those in the other B c ells forming the same islet. 'Potentiators' of insulin secretion include ch olecystokinin (CCK) and acetylcholine (ACh), and exert their effects via th e activation of heterotrimeric G protein-coupled receptors, G(q), in B cell s. The binding of ACh or CCK with G(q) causes protein kinase C (PKC) transl ocation, which results in [Ca2+](c) increase via the steps identical to tho se in the pancreatic acinar cell shown below. The synchrony in periodical [ Ca2+](c) increases observed in glucose-stimulated B cells may be due to cur rent propagation through intercellular gap junctions and electrical excitab ility of plasma membrane in the B-cell society. The electrical excitability of B cell is a characteristic of the paraneurons, whereas the intercellula r signal propagation via the intercellular gap junctions is a characteristi c in common with cells of endodermal origin. In pancreatic acinus, a cell s ociety of endodermal origin, CCK and ACh are the physiological stimuli whic h activate G(q) receptor to produce inositol 1, 4, 5-trisphosphate [Ins (1, 4, 5) P-3] and recurrent Ca2+ spikes. The propagation of the signals, Ins (1, 4, 5) Pg and Ca2+, is markedly be retarded in the acinus: the time laps e(18 s or longer) among the [Ca2+](c) dynamics in individual acinar cells m ay be consumed during the traverse of the signals through the gap junctions among the electrically unexcitabe cells. The periodical [Ca2+](c) increase s, whether they are synchronous or not, are the cardinal cell signalling (a ) for continuation of responses in individual cells; and (b) for integratio n of individual activities of cells forming the societies of exocrine and e ndocrine pancreas.