Pancreatic Enzyme Synthesis and Secretion Are Independently Regulated by Insulin and Glucocorticosteroids

Abstract

Both insulin and glucocorticosteroid (GS) deficiency causes a reduction of amylase synthesis and changes in the dose-response curve of cholecystokinin (CCK) stimulated enzyme secretion in rats. Since we found a reduction of plasma insulin in adrenalectomized rats, we now tested the hypothesis that the regulation of amylase synthesis by insulin may be mediated by GS. Three groups of male rats were investigated: controls, streptozotocin induced diabetics, and diabetics treated with GS. Animals were sacrificed 10-14 days after injection of streptozotocin and isolated pancreatic acini prepared by collagenase digestion. Protein synthesis was measured on the translational level by incubation of acini with 35S-methionine followed by lysis of cells and separation of proteins by SDS-PAGE. In addition, protein synthesis was measured on the transcriptional level by isolation of mRNA from pancreatic acini and translation of proteins using the rabbit reticulocyte lysate system. The loss of insulin in diabetic rats was associated with a 70-90% decrease in amylase synthesis and increases of synthesis of various proteases. This was due to a specific decrease in mRNA coding for amylase and increase in mRNA coding for proteases. Furthermore, the known rightward shift of the dose response curves of CCK stimulated amylase secretion was seen in diabetic animals. Treatment of diabetic rats with GS did deteriorate the catabolic status seen in diabetes with increases in mortality as compared to diabetes alone. However, neither the overall pattern of enzyme synthesis seen in diabetic rats nor the alterations in CCK stimulated enzyme secretion were changed by treatment with GS. We conclude that the regulation of amylase synthesis and enzyme secretion by insulin is not mediated via GS.