MECHANISM OF ACTION OF INSULIN ON PANCREATIC EXOCRINE SECRETION IN PERFUSED RAT PANCREAS

In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h, respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 mi for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM in = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action. Moreover, the reciprocal action between local somatostatin and insulin appears to play a role in the mechanism of action of insulin on pancreatic secretion.