A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of langerhans

Kitsou-Mylona, Isidora and Burns, Christopher and Squires, Paul and Persaud, Shanta and Jones, Peter (2008) A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of langerhans. Cellular Physiology and Biochemistry, 22 (5-6). pp. 557-566. ISSN 1015-8987

Full content URL: http://dx.doi.org/10.1159/000185540

Documents
CPB-2008-CaR.pdf
[img]
[Download]
[img]
Preview
PDF
CPB-2008-CaR.pdf - Whole Document

271kB
Item Type:Article
Item Status:Live Archive

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 β-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 β-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 β-cell to β-cell interactions within islet-like structures.

Keywords:Diabetes
Subjects:C Biological Sciences > C720 Biological Chemistry
Divisions:College of Science > School of Life Sciences
ID Code:14136
Deposited On:29 May 2014 08:51

Repository Staff Only: item control page