Synchronization of Ca2+-signals within insulin-secreting pseudoislets: effects of gap-junctional uncouplers

Squires, Paul E., Hauge-Evans, A. C., Persaud, S. J. and Jones, P. M. (2000) Synchronization of Ca2+-signals within insulin-secreting pseudoislets: effects of gap-junctional uncouplers. Cell Calcium, 27 (5). pp. 287-296. ISSN 0143-4160

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The secretory response of the intact islet is greater than the response of individual β-cells in isolation, and functional coupling between cells is critical in insulin release. The changes in intracellular Ca2+ (Ca2+(i)) which initiate insulin secretory responses are synchronized between groups of cells within the islet, and gap-junctions are thought to play a central role in coordinating signalling events. We have used the MIN6 insulin-secreting cell line, to examine whether uncoupling gap-junctions alters the synchronicity of nutrient- and non-nutrient-evoked Ca2+ oscillations, or affects insulin secretion. MIN6 cells express mRNA species that can be amplified using PCR primers for connexin 36. A commonly used gap-junctional inhibitor, heptanol, inhibited glucose- and tolbutamide-induced Ca2+-oscillations to basal levels in MIN6 cell clusters at concentrations of 0.5 mM and greater, and it had similar effects in pseudoislets when used at 2.5 mM. Lower heptanol concentrations altered the frequency of Ca2+ transients without affecting their synchronicity, in both monolayers and pseudoislets. Heptanol also had effects on insulin secretion from MIN6 pseudoislets such that 1 mM enhanced secretion while 2.5 mM was inhibitory. These data suggest that heptanol has multiple effects in pancreatic β-cells, none of which appears to be related to uncoupling of synchronicity of Ca2+ signalling between cells. A second gap-junction uncoupler, 18 α-glycyrrhetinic acid, also failed to uncouple synchronized Ca2+-oscillations, and it had no effect on insulin secretion. These data provide evidence that Ca2+ signalling events occur simultaneously across the bulk mass of the pseudoislet, and suggest that gap-junctions are not required to coordinate the synchronicity of these events, nor is communication via gap junctions essential for integrated insulin secretory responses. (C) Harcourt Publishers Ltd 2000.

Keywords:18alpha glycyrrhetinic acid, calcium, glucose, heptanol, insulin, messenger RNA, primer RNA, tolbutamide, animal cell, article, calcium signaling, cell line, cell secretion, cell synchronization, concentration response, controlled study, gap junction, gene expression, human, human cell, insulin release, mouse, nonhuman, pancreas islet beta cell, polymerase chain reaction, priority journal, Administration, Topical, Animals, Anti-Inflammatory Agents, Gap Junctions, Glycyrrhetinic Acid, Humans, Hypoglycemic Agents, Islets of Langerhans, Mice, RNA, Messenger, Tolbutamide, Animalia
Subjects:C Biological Sciences > C990 Biological Sciences not elsewhere classified
Divisions:College of Science > School of Life Sciences
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ID Code:14349
Deposited On:18 Jun 2014 13:44

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