Effect of uremia on nutritionally-induced variations in protein metabolism

The effect of uremia on nutritionally-induced variations in protein metabolism was studied in growing rats with chronic, moderate uremia. Plasma and muscle protein synthetic activities and related values were measured from incorporation rates of 14C-leucine infused over a six-hour period. Synthetic activities were compared in the postabsorptive (2 to 14 hr after feeding) and in the fasting (18 to 24 hr after feeding) states. Differences between uremic and control rats were seen in fasting: plasma and intracellular leucine declined in control rats as fasting developed; they rose in uremic rats. In fasting uremic rats, a smaller percent of leucine efflux from extracellular fluid was used for protein synthesis. In a second study, muscle protein synthesis (Sm) and net urea nitrogen production (UNPr) were compared between control and uremic rats which were a) food-deprived but given carbohydrate for 36 hr, and b) fasted for 36 hr. Fasting, as contrasted with carbohydrate feeding, was associated with depressed muscle protein synthesis and increased UNPr in both control and uremic rats; the changes were greater in uremic rats. We conclude that food deprivation for more than 14 hr incurred greater catabolic responses of body protein in moderately uremic rats. The effect was mediated in part by greater suppression of muscle protein synthesis. In contrast, moderate uremia had little discernible effect upon protein metabolism in the postabsorptive state or food deprived state when gluconeogenesis was suppressed with glucose administration.