Gustavson Stephanie M, Sandoval Darleen A, Ertl Andrew C, Bao Shichun, Raj Satish R, Davis Stephen N
Department of Medicine, Div. of Diabetes, Endocrinology, and Metabolism,Vanderbilt University Medical Center 7465 MRB IV, Nashville, TN 37232-0475, USA.
Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E506-12. doi: 10.1152/ajpendo.00589.2007. Epub 2008 Jan 8.
Antecedent increases of corticosteroids can blunt counterregulatory responses to subsequent stress. Our aim was to determine whether prior activation of type I corticosteroid (mineralocorticoid) or type II corticosteroid (glucocorticoid) receptors blunts counterregulatory responses to subsequent hypoglycemia. Healthy volunteers participated in five randomized 2-day protocols. Day 1 involved morning and afternoon 2-h hyperinsulinemic (9 pmol.kg(-1).min(-1)) euglycemic clamps (PE; n = 14), hypoglycemic clamps (PH; n = 14), or euglycemic clamps with oral fludrocortisone (PE + F; type I agonist, 0.2 mg, n = 14), oral dexamethasone (PE + D; type II agonist, 0.75 mg, n = 13), or both (PE + F + D; n = 14). Day 2 was identical in all protocols and consisted of a 2-h hyperinsulinemic hypoglycemic clamp. Day 2 insulin (625 +/- 40 pmol/l) and glucose (2.9 +/- 0.1 mmol/l) levels were similar among groups. Levels of epinephrine, norepinephrine, glucagon, growth hormone, and MSNA were significantly blunted by prior activation of both type I and type II corticosteroid receptors to PE. Prior activation of both corticosteroid receptors also significantly blunted NEFA during subsequent hypoglycemia. Thus, levels of a wide spectrum of key counterregulatory mechanisms (neuroendocrine, ANS, and metabolic) were blunted by antecedent pharmacological stimulation of either type I or type II corticosteroid receptors in healthy man. These data suggest that activation of type I corticosteroid receptors in man can have acute and profound regulating effects on physiological stress in man. Both type I and type II corticosteroid receptors may be involved in the multiple mechanisms controlling counterregulatory responses to hypoglycemia in healthy man.
先前使用皮质类固醇会减弱对随后应激的反调节反应。我们的目的是确定I型皮质类固醇（盐皮质激素）或II型皮质类固醇（糖皮质激素）受体的预先激活是否会减弱对随后低血糖的反调节反应。健康志愿者参与了五个随机的为期2天的方案。第1天包括上午和下午2小时的高胰岛素血症（9 pmol·kg⁻¹·min⁻¹）正常血糖钳夹（PE；n = 14）、低血糖钳夹（PH；n = 14），或口服氟氢可的松的正常血糖钳夹（PE + F；I型激动剂，0.2 mg，n = 14）、口服地塞米松（PE + D；II型激动剂，0.75 mg，n = 13），或两者联合（PE + F + D；n = 14）。所有方案的第2天均相同，包括2小时的高胰岛素血症低血糖钳夹。第2天各组的胰岛素（625±40 pmol/l）和葡萄糖（2.9±0.1 mmol/l）水平相似。I型和II型皮质类固醇受体对PE的预先激活均显著减弱了肾上腺素、去甲肾上腺素、胰高血糖素、生长激素和肌肉交感神经活动（MSNA）的水平。两种皮质类固醇受体的预先激活在随后的低血糖期间也显著减弱了非酯化脂肪酸（NEFA）。因此，在健康男性中，I型或II型皮质类固醇受体的先前药理学刺激会减弱广泛的关键反调节机制（神经内分泌、自主神经系统和代谢）的水平。这些数据表明，男性中I型皮质类固醇受体的激活可对人体生理应激产生急性和深远的调节作用。I型和II型皮质类固醇受体可能都参与了健康男性中控制对低血糖反调节反应的多种机制。
