Extremity amino acid metabolism during starvation and intravenous refeeding in humans

Abstract

This study was designed to evaluate peripheral tissue amino acid metabolism in normal subjects who underwent starvation followed by intravenous administration of a nutritional repletion regimen with varying nonprotein caloric sources. Extremity amino acid (AA), arteriovenous differences, and blood flow were measured across forearm and/or leg of 12 healthy male subjects. Plasma AA flux [(arterial concentration - venous concentration) X flow X (1 - hematocrit); ml X min-1 X 100 ml tissue-1] was determined postabsorptively (PA), after 10 days of starvation (ST) and on the 10th day of intravenous feeding (IVF). There was a significant (P less than 0.05) decrease in efflux of total amino acids during the starvation study (-345 +/- 74) compared with the PA study (-1,463 +/- 263). Peripheral tissue AA uptake increased significantly (P less than 0.05) after 10 days of IVF (+276 +/- 79) compared with both PA and ST studies. There were no significant differences in extremity AA flux between those subjects who received 100% dextrose and those receiving 50% dextrose-50% lipid as a nonprotein caloric source. Linear relationships of AA infusion rate (IR) to AA flux (r = 0.845, P less than 0.001) and AA IR to [AA]art IVF (r = 0.842, p less than 0.001) were observed during IVF. Results of this study suggest that extremity flux determinations during IVF cannot be interpreted without correction for AA availability as reflected by AA infusion rate.

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

“…On day 10 of refeeding, prior to GH infusion, the isolated lower extremity was in net negative amino acid balance, despite concurrent positive body nitrogen balance. This is consistent with previous observations demonstrating that hypercaloric feeding can replete total body nitrogen stores without specifically restoring skeletal muscle protein mass in hospitalized patients (23,24). Following Met-hGH infusion, there was a marked increase in lower extremity amino acid uptake (Fig.…”

“…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).…”

Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury

“…Baseline apoptosis of cultured rat cardiomyocytes was 12.0% ± 1.9%, which increased to 24.2% ± 2.2% (P = 0.0001) after 3 hours of hypoxic challenge (see Methods) as assessed by FITC-conjugated annexin V staining, consistent with prior studies (20). Cell growth media was supplemented with candidate coronary sinus-enriched metabolites at the time of onset of hypoxia at concentrations approximately 2- to 10-fold those previously reported in the plasma (21)(22)(23)(24)(25). Figure 4A shows the percent change in apoptosis relative to the hypoxia control for the lowest concentration of each metabolite screened.…”

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

“…Previous studies have implied that the administration of small amounts of glucose during fasting [67] and hyperglycemia [299] may be protein sparing. To evaluate the response of peripheral amino acid metabolism during substrate deprivation, normal volunteers underwent a 10-day starvation period, followed by intravenous administration of nutrients containing a fixed amount of amino acids but different non-protein caloric sources (100% dextrose or 50% dextrose and 50% lipid emulsion) [300]. 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).…”