Location of Repository

A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans\ud

By Isidora Kitsou-Mylona, Christopher J. Burns, Paul E. Squires, Shanta J. Persaud and Peter M. Jones

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.\ud \u

Topics: QH301
Publisher: S. Karger AG
OAI identifier: oai:wrap.warwick.ac.uk:407

Suggested articles

Preview

Citations

  1. AM: Expression of the calcium-sensing receptor on human antral gastrin cells in culture. doi
  2. Autocrine anti-apoptotic and proliferative effects of insulin in pancreatic [beta]-cells. doi
  3. (1998). Balandrin MF: Calcimimetics with potent and selective activity on the parathyroid calcium receptor. doi
  4. Bikle DD: The Extracellular Calcium-sensing Receptor Is Required for Calcium-induced Differentiation in Human Keratinocytes. doi
  5. Co-ordinated Ca2+-signalling within pancreatic islets: does [beta]-cell entrainment require a secreted messenger. doi
  6. (1996). Duguid W: Determinants of pancreatic islet mass: a balance between neogenesis and senescence/apoptosis. Diabetes Rev
  7. (1990). EG: Identification of multiple epidermal growth factor-stimulated protein serine/threonine kinases from Swiss 3T3 cells.
  8. (1998). EM: Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel. Glia doi
  9. (2001). Extracellular Calcium Sensing and Extracellular Calcium Signaling. Physiol Rev
  10. Extracellular calcium-sensing receptor induces cellular proliferation and activation of a nonselective cation channel in U373 human astrocytoma cells. doi
  11. Glucose-evoked changes in [K +] and [Ca 2+] in the intercellular spaces of the mouse islet of Langerhans. doi
  12. (1998). Identification and Localization of the Extracellular Calcium-Sensing Receptor in Human Breast. doi
  13. Insulin signalling leading to proliferation, survival and membrane ruffling in C2C12 myoblasts. doi
  14. Involvement of protein kinase C-alpha and -epsilon in extracellular Ca2+ signalling mediated by the calcium sensing receptor. doi
  15. LK: Extracellular Calcium as a Candidate Mediator of Prostate Cancer Skeletal Metastasis. doi
  16. Mitogen-activated protein kinases p42 mapk and p44 mapk are required for fibroblast proliferation. doi
  17. (1999). Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas. doi
  18. (1987). Orci L: Stimulation of insulin secretion reveals heterogeneity of pancreatic B cells in vivo. doi
  19. (1992). Pipeleers D: Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity. doi
  20. Pipeleers DG: Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. doi
  21. PM: A Key Role for {beta}-Cell doi
  22. PM: Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases. doi
  23. PM: An islet is greater than the sum of its parts: the importance of intercellular communication in insulin secretion.
  24. (2005). PM: Cell-tocell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures.
  25. (2008). PM: E-cadherin interactions regulate β-cell proliferation in islet-like structures. Cellular Physiology and Biochemistry doi
  26. PM: ERKs Regulate Cyclic AMP-induced Steroid Synthesis through Transcription of the Steroidogenic Acute Regulatory (StAR) Gene. doi
  27. PM: Homotypic cell contact enhances insulin but not glucagon secretion. doi
  28. PM: MIN6 b-cell-b-cell interactions influence insulin secretory responses to nutrients and non-nutrients. doi
  29. (1999). PM: Pancreatic beta-cell-to-betacell interactions are required for integrated responses to nutrient stimuli: enhanced Ca2+ and insulin secretory responses of MIN6 pseudoislets. doi
  30. R: TRPM4 controls insulin secretion in pancreatic [beta]-cells. doi
  31. (1997). Reconstructing islet function in vitro. doi
  32. (1992). RL: Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology doi
  33. (1998). Rodland KD: Functional Calcium-sensing Receptors in Rat Fibroblasts Are Required for Activation of SRC Kinase and Mitogenactivated Protein Kinase in Response to Extracellular Calcium. doi
  34. Rodland KD: Signal Transduction Mechanisms Linking Increased Extracellular Calcium to Proliferation in Ovarian Surface Epithelial Cells. doi
  35. (2002). Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets. Molecular and Cellular Endocrinology doi
  36. S: Protein phosphorylation in electrically permeabilized islets of Langerhans. Effects of Ca2+, cyclic AMP, a phorbol ester and noradrenaline.
  37. (1997). Seino S: Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin.
  38. SJ: Expression and function of the extracellular calcium-sensing receptor in pancreatic Î-cells. doi
  39. (1989). SL: Time-course of Ca2+-induced insulin secretion from perifused, electrically permeabilised islets of Langerhans: effects of cAMP and a phorbol ester. doi
  40. Slatopolsky E: Sustained Activation of the Extracellular Signalregulated Kinase Pathway Is Required for Extracellular Calcium Stimulation of Human Osteoblast Proliferation. doi
  41. Soybel DI: Intercellular communication mediated by the extracellular calcium-sensing receptor.
  42. The extracellular calcium-sensing receptor on human beta-cells negatively modulates insulin secretion. doi
  43. (1989). The insulin secretory granule. Diabetologia doi
  44. Yamamura K: Establishment of a pancreatic beta cell line that retains glucose- inducible insulin secretion: special reference to expression of glucose transporter isoforms. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.