Regulation of biosynthesis of trypsinogen and chymotrypsinogen by nutritional and hormonal factors in the rat

Abstract. Experimental diabetes is associated with decreased pancreatic amylase activity resulting from reduced amylase synthesis and increased amounts of trypsinogen and chymotrypsinogen. The effects of different diets and of experimental diabetes on the synthesis of chymotrypsinogen and trypsinogen in rat pancreas were studied by measuring the incorporation of [4,5‐3H]leucine into these proteins by specific im‐munoprecipitation and simultaneous determination of the specific radioactivity of the pancreatic leucine pool. In addition the effect of acute glucagon treatment on the synthesis of these enzymes was examined. In rat pancreas two trypsinogens and one chymotrypsinogen were found. There was no precursor‐product relationship between the two trypsinogens. Changes in the rate of synthesis affected both isoenzymes to the same extent. Starvation was associated with a decreased rate of synthesis of total pancreatic protein, chymotrypsinogen and trypsinogen. A protein‐rich diet led to an increased rate of synthesis of chymotrypsinogen and trypsinogen, but not of total protein. A carbohydrate‐rich diet diminished the amounts of pancreatic chymotrypsinogen and trypsinogen and the rates of synthesis of these enzymes, whereas a fat‐rich diet had no significant effects on these parameters. Diabetes was associated with increased amounts of chymotrypsinogen and trypsinogen in the pancreas. This resulted from a dramatic increase in their rates of synthesis, whereas that of total pancreatic protein showed no significant change. The same pattern was observed in diabetic adrenalectomized rats or diabetic rats receiving the same amount of a standard diet as non‐diabetic controls. Treatment of rats with glucagon for 6 or 12 h led to a marked decrease of the amounts of pancreatic zymogens, whereas the rates of synthesis of chymotrypsinogen and trypsinogen were only slightly diminished.