Co-ordinated Ca2+-signalling within pancreatic islets: does β-cell entrainment require a secreted messenger

Squires, Paul E., Persaud, S. J., Hauge-Evans, A. C. , Gray, E., Ratcliff, H. and Jones, P. M. (2002) Co-ordinated Ca2+-signalling within pancreatic islets: does β-cell entrainment require a secreted messenger. Cell Calcium, 31 (5). pp. 209-219. ISSN 0143-4160

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Isolated β-cells are heterogeneous in sensory, biosynthetic and secretory capabilities, however, to enable efficient and appropriate secretion, cellular activity within the intact islet is synchronised. Historically, the entrainment of activity to a common pattern has been attributed to gap-junction mediated cell-to-cell communication. Although clearly influential, the possibility remains for other local synchronising mechanisms. In this study, we have used small clusters of insulin-secreting MIN6 cells to assess how contact-dependent, homotypic interactions between cells influences nutrient- and non-nutrient- evoked Ca2+-handling and insulin secretion, and to determine whether a secreted product plays a role in the synchronisation of oscillatory activity. Tolbutamide evoked a concentration-dependent recruitment of active cells within cell clusters, both in terms of numbers of cells and amplitude of the evoked Ca2+-response. The change in [Ca2+]i was characteristically oscillatory above a mean elevated plateau, and was in phase between member cells of an individual cluster. Even at maximal concentrations (100 μM) some cells within a cluster responded before their immediate neighbours. Subsequent oscillatory behaviour then became entrained between member cells within that cluster. Inhibiting exocytosis using the microtubule inhibitors vincristine and nocodazole, or the adrenergic agent noradrenaline, did not prevent tolbutamide-evoked oscillatory changes in [Ca2+]i but did reduce the probability of obtaining synchronous activity within an individual cluster. Above a threshold glucose concentration, the number of cells secreting insulin increased, without a commensurate change in secretary efficiency. This recruitment of cells secreting insulin mirrored Ca2+ data that showed a glucose-dependent increase in cell number, without a change in the mean basal-to-peak change in [Ca2+]i. Together these data suggest that synchronised behaviour in MIN6 cells is dependent, in part, on a secreted factor that acts in a local paracrine fashion to recruit heterogeneous individual cellular activity into an organised group response. © 2002 Elsevier Science Ltd. All rights reserved.

Keywords:adrenergic receptor stimulating agent, calcium ion, glucose, nocodazole, noradrenalin, tolbutamide, vincristine, animal cell, calcium cell level, calcium signaling, calcium transport, cell activity, cell contact, cell count, cell interaction, cell synchronization, concentration response, controlled study, drug antagonism, exocytosis, insulin release, mouse, nonhuman, osmosis, pancreas islet beta cell, paracrine signaling, priority journal, review, second messenger, Animals, Biological Clocks, Calcium, Cell Communication, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Hypoglycemic Agents, Insulin, Islets of Langerhans, Microtubules, Vincristine
Subjects:C Biological Sciences > C990 Biological Sciences not elsewhere classified
Divisions:College of Science > School of Life Sciences
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ID Code:14326
Deposited On:13 Jun 2014 09:34

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