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. ISSN 1015-8987

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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
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of 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
Date:	9 December 2008
Volume:	Vol.22
Number:	No.5-6
Page Range:	pp. 557-566
Identification Number:	10.1159/000185540
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Diabetes UK, Eli Lilly International Foundation
Grant number:	BDA:RD05/0003080 (Diabetes)
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URI:	http://wrap.warwick.ac.uk/id/eprint/407

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