Protein and substrate metabolism during starvation and parenteral refeeding

Abstract

1. Healthy male volunteers underwent 10 days of hospitalized protein-calorie starvation and a subsequent 10 day repletion phase with complete intravenous nutritional support (IVF). Non-protein calories were provided as either all D-glucose or as 50% D-glucose/50% lipid. 2. In comparison with starvation, whole-body protein breakdown, as assessed by [15N]glycine, [13C]leucine and urinary excretion of 3-methylhistidine (3-MH), was diminished during IVF. The administration of parenteral nutrition did not specifically suppress peripheral tissue protein breakdown, as measured by extremity 3-MH efflux. 3. Despite the differential insulin response to D-glucose/amino acid (50 +/- 6 m-units/ml) as compared with the D-glucose/lipid/amino acid regimen (25 +/- 4 m-units/ml), there was no difference in nitrogen retention between the regimens. Indirect calorimetric determinations revealed that oxidation of substrate during IVF was related to the proportion of D-glucose and lipid infusion.

Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

“…1), but the metabolic changes we observed cannot be attributed solely to hyperinsulinemia. Insulin can stimulate intracellular amino acid transport (29), but prior studies from our laboratory, with subjects made chronically hyperinsulinemic, have shown that further increases in serum insulin levels following additional carbohydrate loads does not appear to increase extremity amino acid uptake (23,30). Moreover, insulin infusion predominantly exerts an anticatabolic effect on muscle protein turnover without significantly stimulating protein synthesis (31).…”

The metabolic role of growth hormone in humans with particular reference to fasting

“…Despite the different substrate composition and the higher insulin levels attained with glucose, there was no significant difference in peripheral amino acid flux (i.e., forearm balance). In a similar study protocol [301] whole-body protein breakdown was decreased following parenteral nutrition in comparison with starvation. Other studies, however, suggest that the decrease in whole-body proteolysis during the infusion of glucose is mediated by increased plasma insulin concentrations and not the ambient glucose concentration or the rate of glucose utilization [302].…”

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

“…The effects of semistarvation on body protein and lipid content have been repeatedly described ( 12,37,38), and based on these and other studies it has been suggested that starvation-elicited responses differ from the metabolic changes of cachexia. During unstressed starvation, lipid is utilized preferentially to protein, which tends to be conserved, but in cachexia there is net catabolism of both lipid and protein.…”