Guy Deanna Aftab, Sandoval Darleen, Richardson M A, Tate Donna, Flakoll Paul J, Davis Stephen N
Division of Pediatric Endocrinology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, USA.
Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E178-86. doi: 10.1152/ajpendo.00310.2004.
Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects.
1型糖尿病患者（T1DM）中，关键的对抗调节激素肾上腺素的急性升高可被多种生理和病理状况所改变。然而，肾上腺素的生理作用在T1DM中是否也会降低尚无定论。因此，本研究的目的是确定健康受试者和T1DM患者对肾上腺素的靶器官（肝脏、肌肉、脂肪组织、胰腺、心血管）反应是否存在差异。34名年龄和体重匹配的T1DM患者（n = 17）和健康受试者（n = 17）进行了两项随机、单盲、持续2小时的高胰岛素正常血糖钳夹研究，分别为输注肾上腺素（Epi）和不输注肾上腺素。每项研究结束时进行肌肉活检。所有组在Epi期间的肾上腺素水平相似（4,039±384 pmol/l）。在葡萄糖钳夹期间，所有组的血糖（5.3±0.06 mmol/l）和胰岛素水平（462±18 pmol/l）也相似。T1DM患者对Epi无胰高血糖素反应，与健康受试者相比显著降低。与T1DM相比，健康受试者在Epi期间最后30分钟的内源性葡萄糖生成显著更高（8.4±1.3 vs. 4.4±0.6 μmol·kg-1·min-1，P = 0.041）。与T1DM相比，健康受试者在Epi时葡萄糖摄取的下降幅度几乎大两倍（分别为Δ31±2 vs. Δ17±2 nmol·kg-1·min-1，P = 0.026）。与健康受试者相比，T1DM患者中甘油、β-羟基丁酸和非酯化脂肪酸（NEFA）的升高均显著更多。健康受试者的收缩压升高幅度更大，但Epi时T1DM患者的舒张压下降幅度更大。与健康受试者相比，T1DM患者在输注肾上腺素期间糖原合酶的降低显著更大。总之，尽管肾上腺素、胰岛素和血糖水平相当，但与T1DM相比，健康受试者的葡萄糖通量、胰高血糖素和心血管反应变化更大。然而，T1DM患者在Epi期间有更大的脂解反应（甘油和NEFA）。因此，我们得出结论，T1DM与健康受试者在肝脏、肌肉、脂肪组织、胰腺和心血管系统中肾上腺素作用的体内生理差异存在显著差异。
Zotero 插件