Regulation of L-Type Pyruvate Kinase Gene Expression by Dietary Fructose in Normal and Diabetic Rats1

Abstract

Previous studies have shown that dietary fructose stimulates expression of the L-type pyruvate kinase gene mainly at the post-transcriptional level in diabetic liver, and that this effect may be mediated by a metabolite common to both fructose and glycerol. In the present work, we carried out further studies on the mechanism of fructose induction of L-type isozyme mRNA in the liver, kidney and small intestine of rats. The L-type isozyme mRNA in the kidney of normal and diabetic rats was increased by dietary fructose, the time course of the increase being similar to that observed in the small intestine and liver. The mRNA was not induced in the kidney by dietary glucose or insulin. Glycerol was also a potent inducer of the mRNA in the kidney and liver, but not in the small intestine. These results show that fructose and glycerol induced increase in the mRNA only in organs in which they were metabolized, and thus support the metabolite hypothesis. No other carbohydrates tested increased the level of mRNA in these tissues, except glucose, which increased the level in the small intestine. Thus a molecule that increase the mRNA level may accumulate significantly during metabolism of only certain carbohydrates. Dietary fructose or glycerol slightly stimulated transcription of the gene for the L-type isozyme in diabetic liver, and also in normal and diabetic kidney, but the magnitudes of increase were much lower than those of the mRNA, confirming our previous findings described above. On the other hand, dietary fructose caused marked stimulation of gene transcription in normal rat liver, although the magnitude of its induction of the mRNA was similar to that in diabetic liver. Insulin treatment of fructose-fed diabetic rats also caused a marked increase in the gene transcription without any concomitant change in the mRNA level. Thus, the mechanism of fructose induction of the L-type pyruvate kinase in diabetic liver, which is similar to that found in the kidney, is different from that in normal liver, and this difference is attributable to the difference in the level of insulin.