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. Copyright 2008 S. Karger AG, Basel.
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. Copyright 2008 S. Karger AG, Basel.
Authors: Erik Bader; Adriana Migliorini; Moritz Gegg; Noah Moruzzi; Jantje Gerdes; Sara S Roscioni; Mostafa Bakhti; Elisabeth Brandl; Martin Irmler; Johannes Beckers; Michaela Aichler; Annette Feuchtinger; Christin Leitzinger; Hans Zischka; Rui Wang-Sattler; Martin Jastroch; Matthias Tschöp; Fausto Machicao; Harald Staiger; Hans-Ulrich Häring; Helena Chmelova; Julie A Chouinard; Nikolay Oskolkov; Olle Korsgren; Stephan Speier; Heiko Lickert Journal: Nature Date: 2016-07-11 Impact factor: 49.962
Authors: Katie Leach; Fadil M Hannan; Tracy M Josephs; Andrew N Keller; Thor C Møller; Donald T Ward; Enikö Kallay; Rebecca S Mason; Rajesh V Thakker; Daniela Riccardi; Arthur D Conigrave; Hans Bräuner-Osborne Journal: Pharmacol Rev Date: 2020-07 Impact factor: 25.468