Department of Physiology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China.
Department of Physiology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China.
Biomed Pharmacother. 2020 Aug;128:110300. doi: 10.1016/j.biopha.2020.110300. Epub 2020 May 30.
To explore whether chronic stress induces imbalance of glucose homeostasis, and to investigate the possible involvement of the renin-angiotensin system (RAS).
Male Sprague-Dawley rats were divided into four groups: control, chronic stress, chronic stress plus low dose candesartan (an angiotensin II receptor-1 blocker, ARB, 5 mg/kg/d, i.p.), chronic stress plus high dose candesartan (15 mg/kg/d, i.p.). Rats were received restraint stress for 14 days. Glucose transporter 2 (GLUT2) mRNA was quantified in liver by real-time polymerase chain reaction. The concentration of glucokinase (GK), glucose-6-phosphatase (G-6-P), glycogen synthase (GS), insulin receptor (ISR), glucocorticoid receptor (GR)-alpha and -beta in liver, hexokinase (HK), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in muscle, and serum insulin were measured by ELISA. Body weights, systolic blood pressure, heart rate and fasting blood glucose were monitored. Glucose tolerance test were performed after 14 days restraint stress.
After 14 days restraint stress, systolic blood pressure, increase of plasma glucose concentration at 15 minutes were higher and the fasting plasma concentration of glucose was lower compared with control group (P < 0.05), which were reversed by high dose ARB treatment (P < 0.05). In addition, chronic stress decreased expression of GLUT2 and increased expression of GR beta in liver. High dose ARB treatment normalized GLUT2 and GR beta expressions in liver.
Our present data indicate chronic stress induces the imbalance of glucose homeostasis and RAS contributes to the imbalance of glucose homeostasis induced by chronic stress.
探讨慢性应激是否导致葡萄糖稳态失衡，并研究肾素-血管紧张素系统（RAS）的可能参与情况。
雄性 Sprague-Dawley 大鼠分为四组：对照组、慢性应激组、慢性应激加低剂量坎地沙坦（血管紧张素 II 受体 1 阻滞剂，ARB，5mg/kg/d，腹腔注射）组和慢性应激加高剂量坎地沙坦（15mg/kg/d，腹腔注射）组。大鼠接受 14 天束缚应激。实时聚合酶链反应定量检测肝脏葡萄糖转运蛋白 2（GLUT2）mRNA。通过 ELISA 测定肝组织中葡萄糖激酶（GK）、葡萄糖-6-磷酸酶（G-6-P）、糖原合酶（GS）、胰岛素受体（ISR）、糖皮质激素受体（GR）-α和 -β，肌肉组织中的己糖激酶（HK）、乳酸脱氢酶（LDH）和琥珀酸脱氢酶（SDH），以及血清胰岛素的浓度。监测体重、收缩压、心率和空腹血糖。在 14 天束缚应激后进行葡萄糖耐量试验。
经过 14 天束缚应激，与对照组相比，收缩压升高，15 分钟时血浆葡萄糖浓度升高，空腹血糖浓度降低（P<0.05），高剂量 ARB 治疗可逆转上述变化（P<0.05）。此外，慢性应激降低了肝脏中 GLUT2 的表达，增加了 GRβ的表达。高剂量 ARB 治疗使肝脏中 GLUT2 和 GRβ的表达恢复正常。
我们目前的数据表明，慢性应激导致葡萄糖稳态失衡，RAS 有助于慢性应激引起的葡萄糖稳态失衡。
