Expression of the calcium-sensing receptor in pancreatic islet B-cells.

Exposure of pancreatic islet B-cells to D-glucose and many other insulinotropic agents results in an increase of cytoplasmic calcium concentration, which triggers the exocytosis of secretroy granules. Previous studies have demonstrated that calcium itself, at concentrations ranging from 2 to 18 mM, is able to induce a dose-related stimulation of insulin secretion, even in the absence of any other secretagogue. It was recently demonstrated that parathyroid cells and several other cell types, whether involved or not in calcium homeostasis, sense extracellular calcium through a G-protein coupled calcium-sensing receptor (CaSR). In the present study, the presence of the receptor in islet pancreatic B-cells was scrutinized. Using reverse transcriptase-polymerase chain reaction and Northern blot analysis, we demonstrate the expression of the CaSR in purified rat pancreatic islet B-cells. The nucleotide sequences of the rt-PCR products demonstrated more than 99% homology with the rat kidney CaSR complementary DNA. A specific 5.3 kb transcript of the CaSR was expressed in normal pancreatic B-cells as well as in tumoral insulin-secreting cells. In pancreatic islets, the physiological role of the CaSR in the regulation of insulin release could involve the sensing of endogenous ligands other than calcium.