Effects of islet hormones on amylase secretion and localization of somatostatin binding sites

The interaction of insulin and somatostatin on amylase secretion was examined in the isolated perfused rat pancreas. Exogenous insulin (10 mU/ml) significantly potentiated cholecystokinin- (CCK; 0.5 mU/ml) stimulated amylase secretion (12.47 ± 2.9 μg/ml, n = 7). Glucose (16.7 mM) stimulated endogenous insulin secretion (523 ± 66 μU/ml) and also significantly enhanced CCK-stimulated amylase secretion (13.41 ± 2.8 μg/ml, n = 11). When somatostatin was included in the perfusion media, containing insulin and CCK, amylase secretion was reduced to 3.17 ± 0.83 μg/ml (n = 7), a level comparable to that of CCK-stimulated amylase secretion alone. Similarly, addition of exogenous somatostatin to perfusion media, containing 16.7 mM glucose and CCK, reduced amylase secretion to 4.29 ± 1.09 μg/ml (n = 9). The effect of somatostatin and insulin on carbamylcholine-stimulated amylase secretion was also examined. Exogenous insulin (50 mU/ml) potentiated carbamylcholine- (10^-8 M) stimulated amylase secretion, and addition of exogenous somatostatin to the media containing both insulin and carbamylcholine suppressed the insulin potentiation. Uptake of ¹²⁵I-[Tyr¹¹]somatostatin in the perfused pancreas was saturable as it decreased significantly with the addition of excess unlabeled somatostatin. Autoradiograms revealed uptake of the ligand by both the endocrine islets and the exocrine pancreas with the highest density of grains observed over the acini. These results support the hypothesis that islet peptides modulate the exocrine pancreas, that somatostatin inhibits amylase secretion by inhibiting the action of insulin, and that somatostatin may act directly on the exocrine pancreas via specific receptors on acinar cells.