The role of insulin in the regulation of -amylase synthesis in the rat pancreas.

Abstract

Abstract. Changes in pancreatic exocrine enzyme activities were studied in different forms of experimental diabetes in rats. The effects of adrenalectomy on these changes were measured. The early actions of insulin on pancreatic enzyme activities and on incorporation of (4,5‐3H)‐leucine into amylase were also determined. The main results are: Alloxan‐diabetes leads to a decrease in amylase activity, a decreased rate of amylase synthesis and an increase in the activities of trypsinogen and chymotrypsinogen as described by Palla et al. [9]. Only the decrease in amylase activity correlates with the increase in blood glucose concentration. Adrenalectomy does not reverse the changes in the activities of exocrine pancreatic enzymes induced by diabetes. Diazoxide‐diabetes is accompanied by an increase in all pancreatic enzyme activities, most probably due to the inhibition of enzyme secretion. After treatment with streptozotozin a significant decrease in pancreatic amylase activity appears after 36 h. Amylase activity continues to fall during the following days, in contrast the increase in the activities of proteolytic enzymes is not significant until the 4th day. Insulin treatment of severely diabetic, non‐ketotic rats leads, as early as 90 min. after injection, to a significant increase in pancreatic amylase activity with no change in the other exocrine enzyme activities. A decrease in all enzyme activities, seen 6 h after insulin, is due to enhanced enzyme secretion. As soon as 2 h after injection insulin leads to a significant increase in the incorporation of (4,5‐3H)‐leucine into pancreatic amylase but not into total pancreatic protein. This increase is completely abolished by actinomycin D. Short‐term effects of adrenalectomy (20 h) and effects of substitution with 6‐α‐fluoro‐16α‐methyl‐prednisolon on the incorporation of (4,5‐3H)‐leucine into pancreatic amylase and total pancreatic protein result mainly from changes in the size of the cold leucine pool. According to these results insulin regulates pancreatic amylase synthesis mainly at the level of transcription. Insulin plays a permissive role in pancreatic amylase synthesis and is not involved in short‐term regulation of amylase synthesis in the non‐diabetic state. Clinical findings in juvenile diabetics indicate a similar type of regulation for amylase synthesis.