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 ml 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 (n = 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
K Y
KY
Division of Gastroenterology and Hepatology, Center for Digestive and Liver Diseases, University of Rochester School of Medicine and Dentistry, New York 14642.
Lee
Y L
YL
Kim
C D
CD
Chang
T M
TM
Chey
W Y
WY
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D004338:Drug Combinations; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D007328:Insulin / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D010179:Pancreas / Q000378:metabolism*; D010477:Perfusion; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000494:pharmacology; D013004:Somatostatin / Q000097:blood / Q000502:physiology
D004338:Drug Combinations; D007328:Insulin; D012633:Secretin; D013004:Somatostatin; D002766:Cholecystokinin