Expression and function of the extracellular calcium-sensing receptor in pancreatic beta-cells.
The extracellular calcium-sensing receptor (CaR) was first identified in tissues involved in systemic Ca2+ homeostasis, where it acts to sense changes in circulating Ca2+. It has since been reported that the CaR is expressed in many tissues that are not associated with Ca2+ homeostasis, including the endocrine cells in pancreatic islets of Langerhans. In the present study we have used an insulin-secreting pancreatic beta-cell line (MIN6) to investigate the expression and function of CaR, using the calcimimetic A568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca2+ ([Ca2+]o). Immunocytochemistry, Western blotting and RT-PCR confirmed the expression of CaR in MIN6 cells. CaR activation was associated with rapid and transient increases in [Ca2+]o, which were accompanied by the initiation of a marked but transient insulin secretory response. Stimulation of beta-cell secretory activity had no detectable effect on CaR mRNA levels, but CaR mRNA was markedly reduced by configuring MIN6 cells into islet- like structures. Our data are consistent with an important function for the beta-cell CaR in cell - cell communication within islets to co-ordinate insulin secretory responses.
Jones
Peter M
PM
Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, King's College London, London, UK. peter.jones@kcl.ac.uk
Kitsou-Mylona
Isidora
I
Gray
Elizabeth
E
Squires
Paul E
PE
Persaud
Shanta J
SJ
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D044169:Receptors, Calcium-Sensing