Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells

Abstract

Pancreastatin (PST) is known to inhibit glucose-stimulated insulin release 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 reported on the effect of PST on the intracellular free Ca 2+ concentration ([Ca 2+] i) in pancreatic islet cells. In the present study, by using the dissociated rat pancreatic B-cells, we examined the effects of PST on the increase in [Ca 2+] i induced by several insulin secretagogues, and compared them with those of somatostatin (SRIF). PST (1–100 nM) dose-dependently inhibited the glucose-induced rise in [Ca 2+] i in single pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-induced rise in [Ca 2+] i. These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 μM) with 5.5 mM glucose induced a biphasic increase in [Ca 2+] i in single islet cells. SRIF (10 nM) suppressed the second phase in [Ca 2+] i increase without affecting the first phase. In contrast, PST (100 nM) had no effect on the ACh-induced response. Gastric inhibitory polypeptide (100 nM) with 5.5 mM glucose induced a rise in [Ca 2+] i in single islet cells. SRIF inhibited this increase, but PST did not. Both PST and SRIF failed to affect the sustained rise in [Ca 2+] i evoked by excess K +. These results suggest that PST and SRIF suppress the glucose-induced insulin secretion at least partly by inhibiting the rise in [Ca 2+] i in pancreatic B-cells. Furthermore, PST may suppress the glucose-induced rise in [Ca 2+] i via a mechanism different from that of SRIF.