Bolli G, de Feo P, Compagnucci P, Cartechini M G, Angeletti G, Santeusanio F, Brunetti P
Diabetes. 1982 Jul;31(7):641-7. doi: 10.2337/diab.31.7.641.
During hypoglycemia induced by an i.v. insulin infusion for 60 min, rates of plasma glucose (PG) decrease and recovery, PG nadir, and plasma counter-regulatory hormone and free fatty acid responses were studied in eight type I uncomplicated diabetic subjects and eight nondiabetic subjects. Each subject was tested three times at two different rates of insulin infusion (25 and 32 mU/m2/min): (1) during infusion of saline, (2) during infusion of phentolamine + propranolol (combined alpha, beta-blockade), and (3) during infusion of propranolol alone (isolated beta-blockade) for 150 min. At the time of the studies, the diabetic subjects had been made euglycemic by an overnight i.v. insulin infusion. During infusion of insulin (25 mU/m2/min) and saline, the rates of PG decrease and recovery were slower (P less than 0.01) and PG nadir was delayed in the diabetic subjects. Moreover, their plasma glucagon response was blunted while plasma epinephrine, norepinephrine, growth hormone, and cortisol responses were similar in both groups. Infusion of insulin at 32 mU/m2/min caused larger decreases in PG than had been observed when insulin was infused at 25 mU/m2/min. Plasma glucagon responses increased in the nondiabetic subjects (P less than 0.05) but not in the diabetic subjects. However, in the diabetic subjects, plasma epinephrine increased more than in the nondiabetic subjects (P less than 0.05). There was an inverse correlation between the individual plasma epinephrine responses and the plasma glucagon responses in the diabetic subjects (r = -0.72) but not in the nondiabetic subjects. Alpha, beta-adrenergic blockade decreased the plasma glucose nadir and impaired the rate at which normoglycemia was restored in the diabetic subjects (P less than 0.005 vs. saline) but not in the nondiabetic subjects. Plasma catecholamine and growth hormone responses were increased and plasma FFA recovery was suppressed in both groups (P less than 0.05 vs. saline), while the cortisol responses were unaltered. During isolated beta-adrenergic blockade, changes in plasma glucose, counterregulatory hormones and FFA were essentially identical to those observed during combined alpha, beta-adrenergic blockade in both groups except that the augmented plasma norepinephrine responses were no longer apparent.
although epinephrine is not essential for prompt restoration of normoglycemia in normal man following insulin-induced hypoglycemia, it plays a major role in glucose counterregulation in diabetics who have an impaired glucagon secretion in response to hypoglycemia. These counterregulatory effects of epinephrine are mediated by beta-adrenoreceptors.
在通过静脉输注胰岛素60分钟诱导的低血糖期间，研究了8名I型无并发症糖尿病患者和8名非糖尿病患者的血浆葡萄糖（PG）下降和恢复速率、PG最低点以及血浆反调节激素和游离脂肪酸反应。每个受试者以两种不同的胰岛素输注速率（25和32 mU/m2/分钟）进行三次测试：（1）在输注生理盐水期间，（2）在输注酚妥拉明+普萘洛尔（联合α、β受体阻滞剂）期间，以及（3）在单独输注普萘洛尔（单独β受体阻滞剂）期间，持续150分钟。在研究时，糖尿病患者通过过夜静脉输注胰岛素已实现血糖正常。在输注胰岛素（25 mU/m2/分钟）和生理盐水期间，糖尿病患者的PG下降和恢复速率较慢（P<0.01），PG最低点延迟。此外，他们的血浆胰高血糖素反应减弱，而两组的血浆肾上腺素、去甲肾上腺素、生长激素和皮质醇反应相似。以32 mU/m2/分钟的速率输注胰岛素导致的PG下降幅度大于以25 mU/m2/分钟输注胰岛素时观察到的幅度。非糖尿病患者的血浆胰高血糖素反应增加（P<0.05），而糖尿病患者则没有。然而，在糖尿病患者中，血浆肾上腺素的增加幅度大于非糖尿病患者（P<0.05）。糖尿病患者个体的血浆肾上腺素反应与血浆胰高血糖素反应之间存在负相关（r = -0.72），而非糖尿病患者则不存在。α、β肾上腺素能阻断降低了糖尿病患者的血浆葡萄糖最低点，并损害了血糖恢复正常的速率（与生理盐水相比，P<0.005），而非糖尿病患者则没有。两组的血浆儿茶酚胺和生长激素反应均增加，血浆FFA恢复受到抑制（与生理盐水相比，P<0.05），而皮质醇反应未改变。在单独的β肾上腺素能阻断期间，两组血浆葡萄糖、反调节激素和FFA的变化与联合α、β肾上腺素能阻断期间观察到的变化基本相同，只是血浆去甲肾上腺素反应增强不再明显。
虽然肾上腺素对于正常人在胰岛素诱导的低血糖后迅速恢复血糖正常并非必不可少，但它在对低血糖反应中胰高血糖素分泌受损的糖尿病患者的葡萄糖反调节中起主要作用。肾上腺素的这些反调节作用是由β肾上腺素能受体介导的。
