Davis S N, Colburn C, Dobbins R, Nadeau S, Neal D, Williams P, Cherrington A D
Department of Medicine and Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Clin Invest. 1995 Feb;95(2):593-602. doi: 10.1172/JCI117703.
The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/- 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes.
本研究的目的是确定灌注脑的血液中胰岛素水平的选择性升高是否是对低血糖反调节反应的决定因素。对15只清醒的禁食18小时的狗进行了实验。在单独的随机研究中，将胰岛素（2 mU/kg每分钟）注入外周静脉（n = 7）或颈总动脉和椎动脉（n = 8）。这导致全身胰岛素血症相当（84±6对86±6微U/ml），但头部的胰岛素水平不同（分别为84±6对195±5微U/ml）。在外周胰岛素输注期间输注葡萄糖以将血糖水平维持在与头部胰岛素输注期间所见相似的值（56±2 mg/dl）。尽管外周胰岛素水平相当且低血糖相似，但在头部胰岛素输注期间，稳态血浆肾上腺素（792±198对2394±312 pg/ml）、去甲肾上腺素（404±33对778±93 pg/ml）、皮质醇（6.8±1.8对9.8±1.6微克/dl）和胰多肽（722±273对1061±255 pg/ml）水平均有更大程度的升高（P < 0.05）。用[3-3H]葡萄糖测量的肝葡萄糖生成，在头部胰岛素输注时从2.6±0.2升至4.3±0.4 mg/kg每分钟（P < 0.01），但在外周胰岛素输注期间保持不变（2.6±0.5 mg/kg每分钟）。同样，与外周胰岛素输注相比，头部胰岛素输注期间糖异生、脂肪分解和生酮作用增加了两倍（P < 0.001）。与外周胰岛素输注相比，头部胰岛素输注期间心血管参数也显著更高（P < 0.05）。我们得出结论，在清醒狗的低血糖期间，（a）脑对胰岛素的生理升高直接有反应，并且（b）该反应包括自主神经系统的深刻刺激以及伴随的代谢和心血管变化。
