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A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans
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Kitsou-Mylona, Isidora, Burns, Christopher J., Squires, Paul E., Persaud, Shanta J. and Jones, Peter M. (2008) A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans. Cellular Physiology and Biochemistry, Vol.22 (No.5-6). pp. 557-566. doi:10.1159/000185540 ISSN 1015-8987.
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Official URL: http://dx.doi.org/10.1159/000185540
Abstract
Background: The extracellular calcium-sensing receptor (CaR) is expressed in many tissues that are not associated with Ca2+ homeostasis, including the endocrine cells in pancreatic islets of Langerhans. We have demonstrated previously that pharmacological activation of the CaR stimulates insulin secretion from islet -cells and insulin-secreting MIN6 cells. Methods: In the present study we have investigated the effects of CaR activation on MIN6 cell proliferation and have used shRNA-mediated CaR knockdown to determine whether the CaR is involved in the regulation of insulin secretion via cell-cell communication. Results: CaR activation caused the phosphorylation and activation of the p42/44 MAPK signalling cascade, and this activation was prevented by the shRNA-induced down-regulation of CaR mRNA expression. CaR activation also resulted in increased proliferation of MIN6 cells, consistent with the known role of the p42/44 MAPK system in the regulation of -cell proliferation. Down-regulation of CaR expression had no detectable effects on glucose-induced insulin secretion from MIN6 cells maintained as monolayers, but blocked the increases in insulin secretion that were observed when the cells were configured as three-dimensional islet-like structures (pseudoislets), consistent with a role for the CaR in cell-cell communication in pseudoislets. Conclusion: It is well established that islet function is dependent on communication between islet cells and the results of this study suggest that the CaR is required for -cell to -cell interactions within islet-like structures.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
Library of Congress Subject Headings (LCSH): | Pancreatic beta-cells, Calcium -- Receptors | ||||
Journal or Publication Title: | Cellular Physiology and Biochemistry | ||||
Publisher: | S. Karger AG | ||||
ISSN: | 1015-8987 | ||||
Official Date: | 9 December 2008 | ||||
Dates: |
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Volume: | Vol.22 | ||||
Number: | No.5-6 | ||||
Page Range: | pp. 557-566 | ||||
DOI: | 10.1159/000185540 | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Funder: | Diabetes UK, Eli Lilly International Foundation | ||||
Grant number: | BDA:RD05/0003080 (Diabetes) |
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