A Role for the Extracellular Calcium-Sensing Receptor in Cell-Cell Communication in Pancreatic Islets of Langerhans
Year: 2008
Type: article
Abstract: BACKGROUND: The extracellular calcium-sensing receptor (CaR) is expressed in many tissues that are not associated with Ca(2+) 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 beta-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 beta-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 beta-cell to beta-cell interactions within islet-like structures.
DOI: 10.1159/000185540
Authors: Isidora Kitsou-Mylona, Christopher J. Burns, Paul E. Squires, Shanta J. Persaud, Peter M. Jones
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2128492177