Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis

J Clin Invest. 1987 Apr;79(4):1099-103. doi: 10.1172/JCI112924.

Abstract

Chronic renal failure (CRF) is associated with metabolic acidosis and abnormal muscle protein metabolism. As we have shown that acidosis by itself stimulates muscle protein degradation by a glucocorticoid-dependent mechanism, we assessed the contribution of acidosis to changes in muscle protein turnover in CRF. A stable model of uremia was achieved in partially nephrectomized rats (plasma urea nitrogen, 100-120 mg/dl, blood bicarbonate less than 21 meq/liter). CRF rats excreted 22% more nitrogen than pair-fed controls (P less than 0.005), so muscle protein synthesis and degradation were measured in perfused hindquarters. CRF rats had a 90% increase in net protein degradation (P less than 0.001); this was corrected by dietary bicarbonate. Correction of acidosis did not reduce the elevated corticosterone excretion rate of CRF rats, nor did it improve a second defect in muscle protein turnover, a 34% lower rate of insulin-stimulated protein synthesis. Thus, abnormal nitrogen production in CRF is due to accelerated muscle proteolysis caused by acidosis and an acidosis-independent inhibition of insulin-stimulated muscle protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis / metabolism*
  • Animals
  • Blood Urea Nitrogen
  • Insulin / metabolism
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / metabolism
  • Male
  • Muscle Proteins / metabolism*
  • Muscles / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Uremia / metabolism*

Substances

  • Insulin
  • Muscle Proteins