Glycogen metabolism in muscle in uremia

Abstract

The effect of surgical trauma or acute uremia on glycogen metabolism of skeletal muscle was investigated in bilaterally nephrectomized and sham-operated rats. Glycogen content was decreased due to enhanced glycogenolysis (as determined by increased activation of phos- phorylase a 20 and 40 hr after operation) and decreased glycogen synthesis (glycogen synthetase I activity in fasting rats was only about 10% at 20 and 40 hr after operation as compared with control rats). In skeletal muscle of I-strain (phosphorylase kinase deficient) mice, glycogen concentration was 5-fold higher compared with control mice or rats. In contrast to the very low muscle glycogen content in skeletal muscle of acutely uremic fasting rats there was no decrease in muscle glycogen in fasting I-strain mice 8 or 24 hr after bilateral nephrectomy or sham operation, respectively. This indicates a key role for phosphorylase kinase in the pathogenesis of glycogen depletion in acute uremia or in postoperative stress. The feeding of large amounts of serine in combination with a high-calorie, mixed low-protein diet maximally stimulates glycogen synthesis in rat skeletal muscle. In agreement with . these findings, we were able to isolate a protein glycogen complex from rat skeletal muscle 60 hr after bilateral nephrectomy in serine treated animals. Due to a lower phosphorylase a activity in these animals (30%) as compared to nonserine treated rats (70%), flash activation of this enzyme could be induced in the presence of Ca�, � and ATP. Am. J. Cliii. Nut,. 33: 1461-1467, 1980. Studies by Bergstrom and Hultman (1) revealed a substantial decline (60 to 70%) in muscle glycogen stores in patients with acute renal failure. This phenomenon was indepen- dent of the cause of acute renal failure, but its magnitude was highest in patients with postsurgical acute uremia. A comparable low- ering of muscle glycogen was recorded by the same authors in the postoperative course of nonuremic surgical patients (2). In contrast, normal glycogen content was observed in patients with chronic renal failure with serum creatinine levels up to 25 mg/dl (1). In chronic uremic rats (90% nephrectomy) with a mean blood urea nitrogen of 105 mg/dl, the muscle glycogen stores are also normal (3). In addition, these rats had a 3-fold increase of the cyclic AMP dependent protein kinase and doubling of the phosphorylase a activity as compared to sham-operated animals. Simi- larby, the active I-form ofglycogen synthetase was significantly increased. These findings are consistent with an enhanced glycogen turnover in skeletal muscle of chronic uremic rats (3).