EFFECTS OF PANCREASTATIN AND SOMATOSTATIN ON SECRETAGOGUES-INDUCED RISE IN INTRACELLULAR FREE CALCIUM IN SINGLE-RAT PANCREATIC-ISLET CELLS

Pancreastatin (PST) is known to inhibit glucose-stimulated insulin rel ease both in vivo and in vitro, but it has not been determined whether PST acts directly on pancreatic B-cells and no study has been reporte d on the effect of PST on the intracellular free Ca2+ concentration ([ Ca2+](i)) in pancreatic islet cells. In the present study, by using th e dissociated rat pancreatic B-cells, we examined the effects of PST o n the increase in [Ca2+](i) induced by several insulin secretagogues, and compared them with those of somatostatin (SRIF). PST (1-100 nM) do se-dependently inhibited the glucose-induced rise in [Ca2+](i) in sing le pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-in duced rise in [Ca2+](i). These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 mu M ) with 5.5 mM glucose induced a biphasic increase in [Ca2+](i) in sing le islet cells. SRIF (10 nM) suppressed the second phase in [Ca2+](i) increase without affecting the first phase. In contrast, PST (100 nM) had no effect on the ACh-induced response. Gastric inhibitory polypept ide (100 nM) with 5.5 mM glucose induced a rise in [Ca2+](i) in single islet cells. SRIF inhibited this increase, but PST did not. Both PST and SRIF failed to affect the sustained rise in [Ca2+](i) evoked by ex cess K+. These results suggest that PST and SRIF suppress the glucose- induced insulin secretion at least partly by inhibiting the rise in [C a2+](i) in pancreatic B-cells. Furthermore, PST may suppress the gluco se-induced rise in [Ca2+](i) via a mechanism different from that of SR IF.