Beer-Sheva Mental Health Center, The State of Israel Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of Negev, Beer-Sheva, Israel.
J Neuroendocrinol. 2009 Nov;21(11):898-909. doi: 10.1111/j.1365-2826.2009.01913.x. Epub 2009 Sep 1.
Retrospective clinical reports suggesting that traumatic stress populations display an increased propensity for glucose metabolism disorders were examined in a controlled prospective animal model. Stress-induced behavioural and hypothalamic-pituitary-adrenal (HPA) axis response patterns were correlated to central and peripheral parameters of glucose metabolism and signalling, and to body measurements in Sprague-Dawley rats exposed to predator scent stress. Forty days post-exposure, fasting blood glucose and insulin levels, oral glucose tolerance test, body weight and white adipose tissue mass, systemic corticosterone levels and brain expression of insulin receptor (IR) and insulin-sensitive glucose transporter 4 (GLUT4) protein levels were evaluated. In a second experiment inbred strains with hyper- (Fischer) and hypo- (Lewis) reactive HPA axes were employed to assess the association of metabolic data with behavioural phenomenology versus HPA axis response profile. For data analysis, animals were classified according to their individual behavioural response patterns (assessed at day 7) into extreme, partial and minimal response groups. The exposed Sprague-Dawley rats fulfilling criteria for extreme behavioural response (EBR) (20.55%) also exhibited significant increases in body weight, abdominal circumference and abdominal white adipose tissue mass; a hyperglycaemic oral glucose tolerance test; and fasting hyperglycaemia, hyperinsulinaemia and hypercorticosteronemia, whereas minimal responders (MBR) and control animals displayed no such disturbances. Hippocampal and hypothalamic expression of IR and GLUT4 protein were significantly lower in EBR than in MBR and control rats. The inbred strains showed no metabolic differences at baseline. Exposed Fischer rats displayed hyperglycaemia and hyperinsulinaemia, whereas Lewis rats did not. A significant protracted disorder of glucose metabolism was induced by exposure to a stress paradigm. This metabolic response was associated with the characteristic pattern of HPA axis (corticosterone) response, which underlies the behavioural response to stress.
回顾性临床报告表明，创伤后应激人群表现出葡萄糖代谢紊乱的倾向增加，在对照前瞻性动物模型中进行了检查。应激诱导的行为和下丘脑-垂体-肾上腺 (HPA) 轴反应模式与中枢和外周葡萄糖代谢和信号参数以及暴露于捕食者气味应激的 Sprague-Dawley 大鼠的身体测量相关。暴露后 40 天，评估空腹血糖和胰岛素水平、口服葡萄糖耐量试验、体重和白色脂肪组织质量、全身皮质酮水平以及大脑中胰岛素受体 (IR) 和胰岛素敏感葡萄糖转运蛋白 4 (GLUT4) 蛋白水平的表达。在第二个实验中，使用具有高反应性 (Fischer) 和低反应性 (Lewis) HPA 轴的近交系评估代谢数据与行为表现与 HPA 轴反应谱的关联。为了数据分析，根据个体行为反应模式 (在第 7 天评估) 将动物分为极端、部分和最小反应组。符合极端行为反应 (EBR) 标准的暴露 Sprague-Dawley 大鼠 (20.55%) 还表现出体重、腹围和腹部白色脂肪组织质量增加；口服葡萄糖耐量试验高血糖；空腹高血糖、高胰岛素血症和高皮质酮血症，而最小反应者 (MBR) 和对照动物则没有这种紊乱。EBR 大鼠的海马和下丘脑 IR 和 GLUT4 蛋白表达明显低于 MBR 和对照大鼠。近交系在基线时没有表现出代谢差异。暴露的 Fischer 大鼠表现出血糖升高和胰岛素血症，而 Lewis 大鼠则没有。暴露于应激范式后，葡萄糖代谢明显紊乱。这种代谢反应与 HPA 轴 (皮质酮) 反应的特征模式相关，这是应激行为反应的基础。
