Insulin plays a major role in the control of pancreatic
amylase biosynthesis. In this study we determined
glucose metabolism by pancreatic acini as well as the pancreatic content of both
amylase protein and
amylase mRNA during development of
insulin resistance in the obese Zucker rat. At age 4 weeks there were no abnormalities detected in the above parameters, although the obese animals were already hyperinsulinaemic. At 6 weeks
glucose metabolism was decreased by 50% in acini from obese rats, whereas pancreatic
amylase-gene expression was only slightly impaired. At 22 weeks
glucose metabolism was decreased by 50%,
amylase content by 55% and
amylase mRNA by 60% in acinar tissue of obese rats. As expected, hyperinsulinaemia increased markedly with age. Thus development of severe
insulin resistance was associated with impairment of
amylase-gene expression. To decrease
insulin resistance, one group of adult obese rats was treated with
Ciglitazone for 4 weeks. A lowered plasma
insulin concentration without alteration of food intake was taken as evidence of decreased
insulin resistance. This was associated with normalization of
glucose metabolism and a marked increase of both
amylase content of pancreatic tissue and
amylase mRNA. In conclusion, both the increase of
insulin resistance with age and its partial reversal by
Ciglitazone treatment appear to modulate pancreatic
amylase-gene expression in the obese Zucker rat.