INCREASED PROTEOLYSIS - AN EFFECT OF INCREASES IN PLASMA-CORTISOL WITHIN THE PHYSIOLOGIC RANGE
INCREASED PROTEOLYSIS - AN EFFECT OF INCREASES IN PLASMA-CORTISOL WITHIN THE PHYSIOLOGIC RANGE
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DOI：
10.1172/jci111227
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
HAYMOND, MW
中科院分区：
文献类型：
--
作者：
SIMMONS, PS;MILES, JM;HAYMOND, MW
长期暴露于药理量的糖皮质激素导致肌肉萎缩，但血浆皮质醇在生理范围内的变化是否影响人体的氨基酸和蛋白质代谢尚未确定。为了确定血浆皮质醇的生理性增加是否增加了蛋白水解和丙氨酸的从头合成，在8小时输注氢化可的松琥珀酸钠（2 μ g/kg·cm-1）和氢化可的松琥珀酸钠（2 μ g/kg·cm-1）期间，对7名正常受试者进行了2次研究。min）或盐水。用[2 H3]Leu和[2 H3]Ala估计亮氨酸和丙氨酸的出现率（Ra）。使用[15 N]Leu估计亮氨酸N的Ra和亮氨酸N向丙氨酸的转移速率。血浆皮质醇增加（10 . ±. 1到42 .+-. 4 μ g/dl），并且在皮质醇输注期间降低（14 ± 1.4 μ g/dl）。2到10 .+-. 2 μ g/dl）。在生理盐水或皮质醇输注期间，未观察到血浆胰岛素、C肽或胰高血糖素的变化。皮质醇输注期间血浆亮氨酸浓度增加更多（P < 0.05）（120 ± 0.05）。1到203 .+-. 21 μ M）比生理盐水（118 - 154 μ M）更高，这是由于在皮质醇输注期间其Ra增加更大（P < 0.01）（1.47 ± 0.21 μ M）。0.08至1.81 .+-。0.08μ mol/kg·cntdot。皮质醇最小值与1.50 ±。0.08至1.57 .+-. 0.09μ mol/kg·cntdot。min）。亮氨酸NRa从2.35 ± 0.01升高（P < 0.01）。0.12至3.46 .+-。0.24μ mol/kg·cntdot。min，但在盐水输注期间则较少（P < 0.05）（2.43 ± 0.05）。0.17至2.84 ±。0.15μ mol/kg·cntdot。min，P < 0.01）。丙氨酸Ra在皮质醇输注过程中升高（P < 0.05），而在生理盐水输注过程中保持不变。皮质醇作用下，亮氨酸-N转化为丙氨酸的速率和百分比增加（P < 0.05），而生理盐水作用下则无此变化。因此，在生理范围内血浆皮质醇的增加会增加蛋白质水解和丙氨酸（一种潜在的致炎底物）的从头合成。因此，血浆皮质醇的生理变化在调节人体整体蛋白质和氨基酸代谢中起作用。
Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, 7 normal subjects were studied on 2 occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 .mu.g/kg .cntdot. min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]Leu and [2H3]Ala. The Ra of leucine N and the rate of transfer of leucine N to alanine were estimated using [15N]Leu. Plasma cortisol increased (10 .+-. 1 to 42 .+-. 4 .mu.g/dl) during cortisol infusion and decreased (14 .+-. 2 to 10 .+-. 2 .mu.g/dl) during saline infusion. No change was observed in plasma insulin, C-peptide or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P < 0.05) during cortisol infusion (120 .+-. 1 to 203 .+-. 21 .mu.M) than saline (118 to 154 .mu.M) as a result of a greater (P < 0.01) increase in its Ra during cortisol infusion (1.47 .+-. 0.08 to 1.81 .+-. 0.08 .mu.mol/kg .cntdot. min for cortisol vs. 1.50 .+-. 0.08 to 1.57 .+-. 0.09 .mu.mol/kg .cntdot. min). Leucine N Ra increased (P < 0.01) from 2.35 .+-. 0.12 to 3.46 .+-. 0.24 .mu.mol/kg .cntdot. min, but less so (P < 0.05) during saline infusion (2.43 .+-. 0.17 to 2.84 .+-. 0.15 .mu.mol/kg .cntdot. min, P < 0.01). Alanine Ra increased (P < 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol but not during saline infusion, the rate and percentage of leucine N going to alanine increased (P < 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Thus, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.