EFFECT OF ENDOGENOUS INSULIN ON PANCREATIC EXOCRINE SECRETION IN PERFUSED DOG PANCREAS

Canine pancreas was perfused with an intraarterial infusion of Krebs-R inger bicarbonate solution containing 5% dog red blood cells, 0.1% bov ine serum albumin, and 3% dextran at 15 ml/min, while portal effluent was continuously collected. Pancreatic juice was obtained in 15-min sa mples via main pancreatic duct cannulation. After a 1-h basal period, secretin and cholecystokinin-8 (CCK), at doses of 2.5 ng . min(-1) eac h, were simultaneously infused for 10 min, with background infusion of a normal rabbit serum (NRS) or an antiinsulin serum (Anti-I) in 5 ml each via a sidearm of the intraarterial catheter. The infusion of secr etin and CCK resulted in a significant increase in pancreatic bicarbon ate and protein secretion during the infusion of NRS, whereas the panc reatic secretory response of bicarbonate and protein was profoundly su ppressed by the infusion of Anti-I in six pancreata so studied. This s uppression by Anti-I coincided with significant increases in somatosta tin and pancreatic polypeptide levels in portal venous effluent. In th ree additional pancreata, simultaneous infusions of Anti-I with antiso matostatin (5 ml) and antipancreatic polypeptide (5 ml) serum failed t o inhibit the pancreatic exocrine secretion. These results indicate th at secretin-and CCK-stimulated pancreatic secretion of bicarbonate and protein depends heavily on local action of insulin. The suppression b y Anti-I of pancreatic secretion is mediated, in part, by local releas es of somatostatin and pancreatic polypeptide. Thus, the insuloacinar axis plays an important regulatory role in pancreatic exocrine secreti on in the dog, and it involves at least three islet hormones including insulin, somatostatin, and pancreatic polypeptide.