Effects of chronic renal failure on the regulation of pyruvate kinase

Abstract

The effects of chronic renal failure on the enzyme activity of pyruvate kinase and the mRNA level of this enzyme were studied in 7 out of 8 nephrectomized rats. The mRNA level was measured by RNA-DNA dot blot hybridization, using cloned pyruvate kinase cDNA as hybridized probe. Neither the activity of M 1-type pyruvate kinase nor the level of this enzyme in rat gastrocnemius muscle was affected by chronic renal failure, whereas l-type pyruvate kinase enzyme activity in uremic rat liver was lower than that in control at both fasted and refed states. The levels of l-type pyruvate kinase mRNA were not different between two groups as the fasted state. Induction of l-type pyruvate kinase mRNA after high carbohydrate diet refeeding was suppressed proportionally to the severity of chronic renal failure, which was expressed by the serum creatine concentrations ( r = −.876, P < .005). These results indicate that the suppression of l-type pyruvate kinase activity in uremia was partly reflected by the decreased accumulation of this enzyme mRNA. There was a significantly negative correlation between l-type pyruvate kinase mRNA levels and plasma glucagon/insulin ratios ( r = −.719, P < .05). Hyperglucagonemia in uremia might play a major role in this suppression.