RESPONSE OF HUMAN INSULINOMA CELLS TO EXTRACELLULAR CALCIUM IS DIFFERENT FROM NORMAL B-CELLS

The preoperative determination of the localization of a small insulino ma is sometimes difficult using routine imaging techniques. We have us ed the selective arterial calcium injection (SACI) test to determine t he location of the tumor preoperatively. The pathophysiologic basis of the SACI test is based on the responsiveness of insulinomas to calciu m injected into the feeding artery. In this study, we demonstrated the in vitro response of the insulinoma cells to the extracellular calciu m challenge by using primary-cultured insulinoma cells. Human insulino ma cells were obtained from three patients. MIN6 cells (normal pancrea tic B cells) were used as a control; their insulin response to various stimuli resembles that of normal B cells. The insulin secretory dynam ics in response to extracellular calcium were observed using a perfusi on system. Second, the change of the concentration of cytosolic free c alcium ([Ca2+](i)) was monitored by fluorometry using fura-2/AM. When the concentration of extracellular calcium ([Ca2+](i)) was changed fro m 2.54 mM to 10 mM, insulin secretion (10- to 18-fold at maximum), fro m the insulinoma cells was markedly increased within 6 min and rapidly returned to the basal level; at the same time, [Ca2+]i was immediatel y elevated and reached a peak within 1 min. In contrast, in the MING c ells, the insulin secretion and [Ca2+](i) were not significantly chang ed when [Ca2+](o) was switched to 10 mM. The results of these in vitro experiments agreed with the clinical results of the SACI test. The po sitive response of the insulinoma to the SACI test is probably due to the different response of insulinoma cells to the extracellular calciu m challenge compared with normal B cells. The role of [Ca2+](i) may be important in the mechanism underlying the SACI test.