Expression and function of the calcium-sensing receptor in pancreatic islets and insulinoma cells.

Abstract

We previously demonstrated that human insulinoma cells express the calcium-sensing receptor (CaR). To investigate the expression of CaR in the human pancreas and to evaluate the differences in responses of human insulinoma cells and normal rat islets to extracellular calcium2+ [Ca2+]o. To evaluate CaR expression in the normal human pancreas, immunohistochemical and reverse transcription polymerase chain reaction studies were performed. To evaluate the response of normal islets and insulinoma cells to changes in the [Ca2+]o concentration, cytosolic free calcium levels were measured by microfluorometry. Because it is difficult to obtain viable normal human islets, we used normal rat islets instead. CaR is expressed in both human pancreatic islets and human insulinoma cells. Microfluorometry showed an increase in the [Ca2+]i level in response to changes in the [Ca2+]o concentration, with a more sensitive response in human insulinoma cells than in normal islets. When 1 micromol/L wortmannin (a selective phosphatidylinositol 3-kinase inhibitor) was added to the perfusion medium, the response disappeared in insulinoma cells but not in islets. Both insulinoma cells and islets expressed CaR; however, the reactivity to changes in the [Ca2+]o concentration was different between them. These findings suggest that the signaling pathways controlling the changes in [Ca2+]i differ between normal rat islets and human insulinoma cells.