[Effect of transcutaneous auricular vagus nerve stimulation on hyperglycemia and insulin receptors expression in impaired glucose tolerance rats]

Zhen Ci Yan Jiu. 2020 Nov 25;45(11):882-7. doi: 10.13702/j.1000-0607.200149.
[Article in Chinese]

Abstract

Objective: To explore the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on blood glucose regulation and the expression of insulin receptors (INR) of hypothalamus, liver and skeletal muscle tissues in impaired glucose tolerance (IGT) rats, so as to reveal its mechanisms underlying improvement of IGT.

Methods: Thirty-six male Wistar rats were randomly divided into control, model, transcutaneous auricular none-vagus nerve stimulation (tnVNS), and taVNS groups (n=9 in each group). The IGT model was established by feeding the rats with high-fat and high-sugar diet for 5 weeks, and subsequent intraperitoneal injection of a dose of streptozotocin (20 mg/kg). Transcutaneous electrostimulation (2 mA, 2 Hz/15 Hz) was applied to auricular concha (taVNS) or auricular margin (tnVNS), respectively. The treatment was conducted for 30 min once daily for 4 weeks. The body weight, fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG) were recorded every week. The contents of plasma insulin (INS), glucagon (GC), glycosylated hemoglobin (GHbA1c) were detected by using enzyme linked immunosorbent assay (ELISA). The expression levels of INR in hypothalamus, liver and skeletal muscle tissues were detected by Western blot.

Results: After modeling, the rats' body weight, the contents of FPG, 2 h PG, GC and GHbA1c were significantly up-regulated (P<0.001, P<0.05, P<0.01), and the content of INS and expression of INR in hypothalamus, liver and skeletal muscle tissues were significantly down-regulated in the model group compared with the control group (P<0.001, P<0.01, P<0.05). Following the treatment, the increased FPG, 2 h PG, GC, and the decreased INS and INR expression of hypothalamus, liver and skeletal muscle tissues were apparently reversed in the taVNS group relevant to the model group (P<0.001, P<0.01, P<0.05). Compared with the tnVNS group, the FPG and 2 h PG contents were considerable decreased, and the content of INS and INR expression of hypothalamus and liver were obviously increased in the taVNS group (P<0.001, P<0.05, P<0.01).

Conclusion: taVNS can improve the blood glucose and insulin sensitivity in IGT rats, which may contribute to its effectiveness in up-regulating the expression of INR in hypothalamus, liver and skeletal muscle tissues.

目的:观察经皮耳穴-迷走神经刺激(taVNS)对糖耐量受损(IGT)模型大鼠血糖调节及下丘脑、肝脏、骨骼肌胰岛素受体(INR)表达的影响,探讨taVNS改善IGT的作用机制。方法:36只雄性Wistar大鼠随机分为正常组、模型组、耳缘-非迷走神经刺激(tnVNS)组、耳穴-迷走神经刺激(taVNS)组,每组9只。正常组予普通饲料喂养,模型组、tnVNS组和taVNS组予高糖高脂饲料喂养联合腹腔注射小剂量链尿佐菌素以制备IGT模型。造模后对tnVNS组和taVNS组大鼠连续干预4周,tnVNS组刺激部位为耳缘区(无迷走神经分布)、taVNS组刺激部位为耳甲区(有迷走神经分布),强度为2 mA,频率为疏密波2 Hz/15 Hz,每次30 min,每天1次,共4周。整个实验持续10周,记录各组大鼠的体质量、空腹血糖(FPG)、餐后2 h血糖(2 h PG),ELISA法,检测血浆胰岛素(INS)、胰高血糖素(GC)、糖化血红蛋白(GHbA1c)水平,Western blot法检测INR在下丘脑、肝脏、骨骼肌中的表达量。结果:造模后与正常组比较,其余3组大鼠体质量均明显增加(P<0.001),FPG和2 h PG升高(P<0.05,P<0.001),符合IGT的诊断标准,提示造模成功。干预后与正常组比较,模型组大鼠体质量明显增加(P<0.001),FPG、2 h PG及GC、GHbA1c含量明显升高(P<0.05,P<0.01),血浆INS含量及下丘脑、肝脏、骨骼肌INR表达明显降低(P<0.001,P<0.01,P<0.05)。干预后与模型组比较,taVNS组大鼠体质量、FPG、2 h PG、血浆GC含量明显降低(P<0.01,P<0.05),INS含量及下丘脑、肝脏、骨骼肌中INR表达明显升高(P<0.001,P<0.01,P<0.05)。干预后与tnVNS组比较,taVNS组大鼠FPG和2 h PG值降低(P<0.05),INS含量及下丘脑、肝脏中INR表达明显升高(P<0.001,P<0.05,P<0.01)。结论:经皮耳穴-迷走神经刺激可调节IGT模型大鼠的FPG和2 h PG,降低GC,提高INS敏感性,上调下丘脑、肝脏、骨骼肌中INR的表达。.

Keywords: 2 h plasma glucose; Fasting plasma glucose; Impaired glucose tolerance; Insulin receptors; Transcutaneous auricular vagus nerve stimulation.

MeSH terms

  • Animals
  • Glucose Intolerance* / genetics
  • Glucose Intolerance* / therapy
  • Hyperglycemia* / genetics
  • Hyperglycemia* / therapy
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Insulin
  • Vagus Nerve Stimulation*

Substances

  • Receptor, Insulin