Endogenous somatostatin inhibits interaction of insulin and cholecystokinin on exocrine secretion of isolated, perfused rat pancreas

Introduction: Although somatostatin inhibits pancreatic exocrine secretion, the inhibitory mechanism of endogenous somatostatin is not clearly understood. Aim: To investigate the effect of endogenous somatostatin on the interaction between endogenous insulin and exogenous cholecystokinin (CCK) in exocrine secretion of the totally isolated, perfused rat pancreas. Methodology: Endogenous releases of somatostatin and insulin were induced by 18 mM glucose. Streptozotocin (75 mg/kg) or cysteamine (300 mg/kg) was injected into rats 24 hours before the experiment to deplete insulin or somatostatin in the pancreas. Results: Glucose (18 mM) enhanced CCK (10 pM)-stimulated secretions of fluid and amylase in the normal pancreas, which was further elevated by a somatostatin antagonist. Exogenous insulin (100 nM) also enhanced CCK-stimulated secretions in the streptozotocin-treated pancreas, which was also markedly increased by the somatostatin antagonist. The glucose (18 mM)-enhanced CCK-stimulated secretions were much higher in the cysteamine-treated pancreas than in the normal pancreas, which was dose-dependently reduced by exogenous somatostatin (30, 100 pM). However, endogenous or exogenous somatostatin did not modify the pancreatic responses to CCK alone. Conclusion: Endogenous somatostatin inhibits the interaction of endogenous insulin and CCK on pancreatic exocrine secretion in the rat rather than reducing the action of CCK alone or endogenous release of insulin.