In Vivo Deactivation of Peripheral, Hepatic, and Pancreatic Insulin Action in Man
In Vivo Deactivation of Peripheral, Hepatic, and Pancreatic Insulin Action in Man
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人体外周、肝脏和胰腺胰岛素作用的体内失活
作者：
R. S. Gray;J. A. Scarlett;J. Griffin;J. Olefsky;O. Kolterman
在10名瘦削的非糖尿病受试者中，使用一种改良的正常血糖葡萄糖钳夹技术研究了体内胰岛素的失活作用。停止40和120mU/m~2/m in胰岛素输注后，血清胰岛素水平在7±1和8±1 m in分别降至初始值的一半，分别为126±7和350±14μU/m l。停用40和120 mU/m~2/min胰岛素后，平均增量葡萄糖处置速率(IGDR)下降较慢，使IGDR降至初始值(D50)的一半所需时间分别为42±5和78±5分钟。平均肝葡萄糖输出量在40和120mU/m~2/min胰岛素输注期间被完全抑制，在停止输注50和80min后仍保持完全抑制状态，随后恢复到基础水平。HGO恢复到基础水平的一半所需时间分别为59±8分钟和119±6分钟。外周(D50IGDR)和肝脏(R50HGO)胰岛素作用降至初始值的一半所需的时间与个体先前的稳态葡萄糖处置速率相关(r=0.75P<；0.001和r=0.58P<；0.05)。在5次正常血糖钳夹试验中，4名受试者也研究了外源性胰岛素对内源性胰岛素分泌的抑制作用；在注射外源性胰岛素之前，血清C肽水平平均为0.67±0.24pmol/ml，在研究的稳态期降至0.34±0.17pmol/ml，并在葡萄糖钳失活阶段一直受到抑制。在葡萄糖钳夹失活期结束时给予标准餐120分钟后，血清C-肽水平上升至1.77±0.50 pmol/ml，显示了残余的胰腺胰岛素分泌能力。这些结果表明，外周、肝脏和胰腺中胰岛素的失活作用滞后于血浆中胰岛素的消失。导致体内失活滞后的机制尚不清楚，但可能包括胰岛素从组织间的清除速度慢于血浆，靶组织必须产生特定的失活信号，或者细胞激活过程中饱和步骤的缓慢衰减。
The in vivo deactivation of insulin action has been studied in 10 lean, nondiabetic subjects using a modification of the euglycemic glucose clamp technique. Following cessation of 40- and 120-mU/m2/min insulin infusions, the serum insulin levels fell to one-half their initial values (mean ± SE) of 126 ± 7 and 350 ± 14 μU/ml in 7 ± 1 and 8 ± 1 min, respectively. The mean incremental glucose disposal rates (IGDR) fell more slowly following discontinuation of the 40- and 120-mU/m2/min insulin infusions, so that the time required for the IGDRs to fall to one-half their initial values (D50 IGDR) were were 42 ± 5 and 78 ± 5 min, respectively. Mean hepatic glucose output was totally suppressed during the 40- and 120-mU/m2/min insulin infusions, remained completely suppressed following cessation of the infusions for 50 and 80 min, and subsequently returned to basal levels. The times required for the HGOs to return to one-half their basal levels (R50 HGO) were 59 ± 8 and 119 ± 6 min, respectively. The times required for insulin action to decrease to one-half the initial values in the periphery (D50 IGDR) and in the liver (R50 HGO) were correlated with the preceding steady-state glucose disposal rates in individual subjects (r = 0.75, P < 0.001 and r = 0.58, P < 0.05, respectively). The suppression of endogenous insulin secretion by exogenous insulin infusions was also studied in 4 subjects during a total of 5 euglycemic glucose clamps; the mean basal serum C-peptide level was 0.67 ± 0.24 pmol/ml before administration of the exogenous insulin, fell to 0.34 ± 0.17 pmol/ml during the steady-state phase of the study, and remained suppressed throughout the duration of the deactivation phase of the glucose clamp. Residual pancreatic insulin secretory capacity was demonstrated by a rise in the serum C-peptide level to 1.77 ± 0.50 pmol/ml at 120 min following a standardized meal given at the conclusion of the deactivation phase of the glucose clamp. These results demonstrate that the deactivation of insulin action in the periphery, liver, and pancreas lags behind the disappearance of insulin from the plasma. The mechanisms responsible for this lag in in vivo deactivation are not known for certain, but may include slower clearance of insulin form tissue compartments than form the plasma, the necessity for the target tissues to generate specific deactivation signals, or a slow rate of decay of saturable steps in the cellular activation process.