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

Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients
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DOI:
10.1152/ajpendo.2000.279.2.e323
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发表时间:
2000-08-01
影响因子:
5.1
通讯作者:
Guarnieri, G
Guarnieri, G
中科院分区:
医学2区
文献类型:
--
作者:
Biolo, G;Iscra, F;Guarnieri, G

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我们确定了24小时重组人生长激素(rhGH)输注到股动脉对腿部肌肉蛋白动力学,氨基酸转运和谷氨酰胺代谢的影响,在8名成人高分解代谢创伤患者。通过腿部动静脉导管插入术和使用稳定氨基酸同位素的肌肉活检评估代谢途径。通过竞争性PCR测定所选酶的肌肉mRNA水平。rhGH输注显著加快了苯丙氨酸和亮氨酸的内向转运速率和蛋白质合成,而肌肉蛋白质降解速率和组织蛋白酶B和Ub B聚泛素mRNA水平未被rhGH显著改变。rhGH输注降低了谷氨酰胺从头合成速率和谷氨酰胺前体可用性、总支链氨基酸催化剂和非蛋白谷氨酸利用率。因此,rhGH给药后,从肌肉释放到循环中的谷氨酰胺净额显著减少(接近50%),而谷氨酰胺合成酶mRNA水平在rhGH输注后增加,可能是为了补偿谷氨酰胺前体可用性的降低。我们的结论是,创伤后,rhGH的抗分解作用与肌肉谷氨酰胺产生的潜在有害减少有关。
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 (similar to 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.