Activity of the Insulo-Acinar Axis in the Isolated Perfused Rat Pancreas*

Abstract

It was determined whether insulin secreted by the endocrine pancreas and carried in the insulo-acinar portal system has a direct effect on pancreatic enzyme secretion. The isolated rat pancreas was perfused in a nonrecirculating system. The perfusate contained 3 mM glucose, and either cerulein or vasoactive intestinal polypeptide was used to stimulate exocrine secretion. The amount of insulin reaching the exocrine pancreas was reduced by 2 different experimental procedures. In the 1st, use was made of streptozotocin-diabetic rats treated with insulin in vivo. Treatment was such that the contents of amylase and lipase, vastly altered in the untreated diabetic state, were normalized before the perfusion studies. in the 2nd procedure, insulin reaching the exocrine pancreas was reduced by antiinsulin serum in the perfusate. In these procedures, the reduced insulin bioavailability was associated with a reduction in cerulein- and vasoactive intestinal polypeptide-stimulated enzyme release, which was shown as a reduction of maximum responsiveness to cerulein without alteration of sensitivity. By contrast, in dispersed pancreatic acini where the insulo-acinar axis was completely disrupted, amylase secretion from diabetic and nondiabetic tissue was identical over a wide range of cerulein concentrations, showing that the secretory defect seen in the perfusion studies was not inherent to the exocrine tissue. Basal insulin secretion has a direct effect on pancreatic enzyme output, and the insulo-acinar axis may play an important role in the regulation of acinar cell function.