Project: Research project

Project Details


This proposal addresses the role of insulin resistance as a factor in the
abnormal protein metabolism of chronic renal failure. Using a
well-characterized muscle perfusion system, I will study uremic and
sham-operated rats to determine dose response curves and degradation
rates. Uremic animals will be studied during perfusion with both
physiologic and pharmacologic concentrations of insulin. Individual rates
of skeletal muscle protein synthesis, total hemicorpus protein and
myofibrillar protein degradation will be determined in both fed and fasted
animals. The site of insulin resistance in uremia will be determined by
examination of the known steps within the pathways of protein synthesis and
degradation. The role of leucine, another regulator of protein turnover
whose site of action cannot be distinguished from that of insulin, will
also be examined. The cause of the insulin resistance, the time course of
its development, and the possible importance of circulating serum factors
will be assessed in independent studies using, where appropriate, "uremic"
perfusate and acutely versus chronically uremic animals. Pair-feeding
studies will be performed to assess the role of undernutrition as opposed
to uremia per se. In a chronically hyperinsulinemic rat model, I will
examine the possibility that weight gain and muscle protein anabolism can
be improved in uremia with exogenous insulin supplementation. Both in vivo
and in vitro studies will compare protein turnover in uremic and in
sham-operated control animals not receiving insulin supplementation. These
studies have a direct bearing upon the abnormal protein metabolism,
diminished weight gain and decreased muscle mass seen in patients,
particularly children, with chronic renal insufficiency. A better
understanding of these abnormalities could lead to improvements in the care
of these individuals as well as a better understanding of the regulation of
protein turnover under diverse physiologic conditions.
Effective start/end date12/31/8912/31/89


  • National Institutes of Health


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