Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients

Abstract

We determined the effects of 24-h recombinant human growth hormone (rhGH) infusion into a femoral artery on leg muscle protein kinetics, amino acid transport, and glutamine metabolism in eight adult hypercatabolic trauma patients. Metabolic pathways were assessed by leg arteriovenous catheterization and muscle biopsies with the use of stable amino acid isotopes. Muscle mRNA levels of selected enzymes were determined by competitive PCR. rhGH infusion significantly accelerated the inward transport rates of phenylalanine and leucine and protein synthesis, whereas the muscle protein degradation rate and cathepsin B and UbB polyubiquitin mRNA levels were not significantly modified by rhGH. rhGH infusion decreased the rate of glutamine de novo synthesis and glutamine precursor availability, total branched-chain amino acid catabolism, and nonprotein glutamate utilization. Thus net glutamine release from muscle into circulation significantly decreased after rhGH administration ( approximately 50%), whereas glutamine synthetase mRNA levels increased after rhGH infusion, possibly to compensate for reduced glutamine precursor availability. We conclude that, after trauma, the anticatabolic action of rhGH is associated with a potentially harmful decrease in muscle glutamine production.

Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery

“…Concentrations of selected amino acids (phenylalanine, leucine, and glutamine) and isotopic enrichment of L-[ring-2 H 5 ]phenylalanine were measured in plasma samples taken from the radial artery and femoral vein, as previously described (21,22). The stable isotopes L- [1-13 C]phenylalanine, L-[1-13 C]leucine, and L- [5-15 N]glutamine were added to the tubes as internal standards (22).…”

“…The stable isotopes L- [1-13 C]phenylalanine, L-[1-13 C]leucine, and L- [5-15 N]glutamine were added to the tubes as internal standards (22). To determine the enrichment of the infused tracer and the internal standards of free phenylalanine, leucine, and glutamine in the plasma, the t-butyldimethylsilyl derivatives were prepared as described by Biolo et al (21). Tracer/tracee ratios were measured by gas chromatography-mass spectrometry analysis (Hewlett-Packard 5985) (21).…”

“…A 2-day crossover experimental design was used to compare the effects of moderate hyperglycemia and euglycemia, resulting from 24 hrs of traditional or intensive insulin treatment, on the rates of skeletal muscle protein synthesis and degradation, leucine oxidation, glutamine de novo synthesis, and dimethylarginine production, as determined by the leg arteriovenous catheterization and stable isotopic tracers (21,22).…”

Short-term application of low-dose growth hormone in surgical patients: Effects on nitrogen balance and blood glucose

“…Recent studies indicated that rhGH had beneficial effects on stimulating body protein syntheses and producing nitrogen-spacing effects [6,[12][13][14] . However, the impact of rhGH on body proteins and the change in blood glucose levels have not been previously investigated in patients receiving PN or EN following elective gastrointestinal surgeries [15][16][17] . In the present experiment, we observed the effect of rhGH on nitrogen balance, plasma proteins and blood glucose levels.…”

Effects of short-term application of low-dose growth hormone on trace element metabolism and blood glucose in surgical patients

“…Recent studies indicate that rhGH can stimulate body protein synthesis and produce nitrogenspacing effects [11][12][13] . However, the impact of rhGH on body trace elements and blood glucose has not been investigated in patients receiving PN or EN following selective gastrointestinal surgery [14][15][16] . In the present experiments, we studied the effects of rhGH on trace element metabolism and blood glucose.…”