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 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 Ca2+ concentration ([Ca2+]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 [Ca2+]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 [Ca2+]i in single pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-induced rise in [Ca2+]i. These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 microM) with 5.5 mM glucose induced a biphasic increase in [Ca2+]i in single 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 polypeptide (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 excess K+. These results suggest that PST and SRIF suppress the glucose-induced insulin secretion at least partly by inhibiting the rise in [Ca2+]i in pancreatic B-cells. Furthermore, PST may suppress the glucose-induced rise in [Ca2+]i via a mechanism different from that of SRIF.
Ma
H T
HT
Department of Molecular Physiology, Gunma University, Japan.
Kato
M
M
Tatemoto
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D053379:Chromogranin A; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D010187:Pancreatic Hormones / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology*
D053379:Chromogranin A; D006727:Hormone Antagonists; D010187:Pancreatic Hormones; C050836:pancreastatin; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D002766:Cholecystokinin; D005947:Glucose; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium