Regulation of rat liver L-type pyruvate kinase mRNA by insulin and by fructose.

The effects have been studied of streptozotocin-induced diabetes and subsequent insulin administration or feeding of a high fructose diet on the amount of enzyme protein and mRNA activity of L-type pyruvate kinase in rat liver. Diabetes markedly decreased the L-type enzyme activity in rat liver and insulin treatment resulted in restoration of the enzyme activity to normal. A high fructose diet also increased the enzyme activity in diabetic rats but to a lesser extent. Immunochemical analysis showed that these alterations in the enzyme activity were due to changes in the amount of immunoreactive enzyme protein. The mechanism of the changes was studied further by assaying the level of functional mRNA coding for this enzyme in a nuclease-treated reticulocyte lysate system with total RNA isolated from rat liver. L-type pyruvate kinase mRNA, expressed as a percentage of the total protein synthesized, was greatly decreased in diabetic rats. Insulin administration resulted in recovery of the mRNA activity to the normal level within 24 h. The lag period before accumulation of translatable mRNA of the L-type enzyme was about 4-5 h. The mRNA activity was also increased in diabetic rats fed a high fructose diet. This fructose effect, which was much smaller than the insulin effect, was maximal after feeding fructose diet for one day. These changes were approximately comparable to the changes in enzyme activity. Thus, it is suggested that regulations of rat liver L-type pyruvate kinase by insulin and by fructose are primarily due to changes in the level of translatable mRNA of this enzyme.