THE EFFECT OF PRETRANSLATIONAL REGULATION ON SYNTHESIS OF PANCREATIC COLIPASE IN STREPTOZOTOCIN-INDUCED DIABETES IN RATS

A significant increase in synthesis of pancreatic colipase in streptozotocin (STZ)-induced diabetes in rats has been demonstrated previously. The aim of the present study was to identify whether this change in colipase synthesis was related to a pretranslational or translational regulation. The levels of colipase, lipase, and amylase mRNA were determined by Northern blot hybridization. The enzymatic activities and synthesis rates for these proteins were determined. One week after injection of STZ, the mRNA levels for both colipase and lipase were increased by about 100% over control, with accompanying increases in enzyme synthesis rates and enzymatic activities. The amylase mRNA, amylase synthesis rates, and amylase activity decreased by 95%. Insulin injection at a dose of 2 U/100 g/day for 5 days restored enzyme mRNA levels as well as enzyme activities. Kinetic studies revealed that lipase mRNA rapidly increased after induction of diabetes, closely followed by increases in lipase synthesis rates and lipase content. Colipase mRNA also rapidly increased, with values 60, 85, and 82% over control 1, 2, and 3 days after STZ injection, respectively. But the colipase synthesis rate increased slowly, being only 10, 20, and 40% over control 1, 2, and 3 days after STZ treatment, respectively. Colipase content did not increase until 4 days after STZ injection (3 days after the increase in colipase mRNA). The decrease in amylase mRNA was paralleled by decreases in amylase synthesis rates and amylase content. In conclusion, the increase in colipase content in STZ-induced diabetes in rats is a consequence of enhanced transcriptional or pretranslational regulation. The asynchronous change of colipase mRNA versus colipase synthesis rate and colipase content indicates that some kind of limitation exists at the translational level for colipase synthesis.