THE REGULATION OF GENE-EXPRESSION BY INSULIN IS DIFFERENTIALLY IMPAIRED IN THE LIVER OF THE GENETICALLY OBESE-HYPERGLYCEMIC WISTAR FATTY RAT

The regulation by insulin and carbohydrates of the gene expression of three key enzymes involved in glucose metabolism was studied in the liver of the Wistar fatty rat, a model of obese non-insulin-dependent diabetes mellitus. A high glucose or fructose diet, or insulin administration caused a similar magnitude of increase in the level of L-type pyruvate kinase mRNA in the liver of Wistar fatty rats and their lean littermates. However, the induction of glucokinase mRNA and repression of phosphoenolpyruvate carboxykinase mRNA by dietary glucose or insulin were impaired in the fatty rats, whereas fructose caused a similar decrease in phosphoenolpyruvate carboxykinase mRNA in both types of rats. These results indicate that the regulation of gene expression of glucokinase and phosphoenolpyruvate carboxykinase, but not of L-type pyruvate kinase, by insulin is impaired in the liver of the Wistar fatty rat.