Role of insulin in the regulation of leucine kinetics in the conscious dog.

Role of insulin in the regulation of leucine kinetics in the conscious dog.
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胰岛素在清醒狗亮氨酸动力学调节中的作用。

DOI:
10.1172/jci110690
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发表时间:
1982
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Lacy,WW
Lacy,WW
中科院分区:
--
文献类型:
--
作者:
Abumrad,NN;Jefferson,LS;Rannels,SR;Williams,PE;Cherrington,AD;Lacy,WW

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为了研究胰岛素对亮氨酸动力学的影响,在禁食过夜(16-18小时)后研究了三组清醒的狗。生理盐水灌注组(n= 5)作为对照。另两组均输注生长抑素和恒定替代量胰高血糖素,其中一组(n= 6)不进行胰岛素替代,产生急性胰岛素缺乏,另一组(n= 6)以600 μU/kg/min的胰岛素持续替代,产生2次基础高胰岛素血症。采用动静脉差分技术计算肝内和肝外内脏(肠道)亮氨酸和α-酮异己酸(KIC)的平衡,用1,4,5,[3 H]亮氨酸测定其比值(微摩尔/千克/分钟)的出现(Ra)和消失(Rd),以及血浆亮氨酸的清除率(Cl)生理盐水输注7 h可达到同位素稳态,Ra和Rd相等(3.2±0.2 μmol/kg/min)。急性停药4 h后,血浆亮氨酸水平升高40%(P< 0.005)。这种变化是由亮氨酸(Cl)从血浆中流出减少引起的,因为Ra没有变化。氨基酸的肝脏净释放(0.24±0.03 μmol/kg/min)没有显著变化;亮氨酸(−10±1 μmol/L)和KIC(−12±2 μmol/L)的动脉-股深静脉差异没有显著变化,表明氨基酸和酮酸在后肢的净释放。选择性两次基础高胰岛素血症导致血浆亮氨酸在4 h内下降36%(从对照水平128±8降至82±7 μmol/L,P< 0.005)。这伴随着Ra降低15%和清除率增加56%(P< 0.001,两者)。肝脏净亮氨酸产量以及后肢净释放的亮氨酸和KIC显着下降。这些研究表明,循环胰岛素水平的生理变化导致对完整动物全身亮氨酸代谢的不同剂量依赖性作用。急性胰岛素戒断对亮氨酸的出现率无影响,而在两倍基础水平时,胰岛素抑制亮氨酸的出现率并促进其消失率。
To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n= 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n= 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n= 6) was constantly replaced with 600 μU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and α-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique.l,4,5,[3H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute).Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2±0.2 μmol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P< 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24±0.03 μmol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (−10±1 μmol/liter) and KIC (−12±2 μmol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128±8 to 82±7 μmol/liter,P< 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P< 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.
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