Zhang Yuzhengheng, Zou Ningyi, Xin Chen, Wang Yifei, Zhang Zixuan, Rong Peijing, Li Shaoyuan
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Front Neurosci. 2024 Nov 5;18:1471387. doi: 10.3389/fnins.2024.1471387. eCollection 2024.
Melatonin (MLT) and its receptor deficiency have been shown to be associated with type 2 diabetes mellitus (T2DM). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive alternative intervention for patients suffering from hyperglycemia. Here, we aimed to investigate the role of taVNS on blood glucose modulation via intestinal melatonin receptors (MRs) and MLT secretion in hyperglycemia.
Adult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. Forty ZDF rats were randomized into ZDF, taVNS, Px + taVNS and Lu + Px + taVNS groups (Px: pinealectomy, Lu: Luzindole). ZL rats served as a control group for comparison with ZDF rats without involvement in the taVNS intervention. Thirty min-taVNS interventions (2/15 Hz, 2 mA, 30 min/days) were administered once daily under anesthesia for 3 consecutive weeks in taVNS, Px + taVNS and Lu + Px + taVNS groups. Body weight and fasting blood glucose (FBG) were measured weekly in all rats, and real-time blood glucose was tested in the ZL and ZDF groups before, during and after the taVNS intervention. Plasma MLT concentration and the expression of MRs in the duodenum, jejunum and ileum were measured by the end of experiments.
Compared with the ZL group, the level of FBG and body weight increased (all < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all < 0.05), respectively. TaVNS can significantly reverse the hyperglycemia by regulating the non-pineal-derived MLT and MRs system in Px + taVNS group. Compared with the ZDF group, the expression of different intestinal MRs in the taVNS group was increased and more compactly arranged (both < 0.05), the level of plasma MLT secretion was up-regulated ( < 0.01), and FBG and body weight were decreased (both < 0.01). Meanwhile, after taVNS intervention in rats in the Px + taVNS group, we observed an increase in MLT secretion and the number of intestinal MRs compared with the taVNS group (all > 0.05). In contrast, ZDF rats in which the pineal gland was excised by taVNS intervention and injected with the MRs antagonist Luzindole did not show these changes.
The glucose reduction effect of taVNS may be related to regulating MLT levels and expressing intestinal MRs.
褪黑素（MLT）及其受体缺乏已被证明与2型糖尿病（T2DM）相关。经皮耳迷走神经刺激（taVNS）是一种针对高血糖患者的非侵入性替代干预措施。在此，我们旨在研究taVNS通过肠道褪黑素受体（MRs）和MLT分泌对高血糖中血糖调节的作用。
使用成年雄性Zucker糖尿病肥胖（ZDF）大鼠和Zucker瘦（ZL）同窝大鼠。40只ZDF大鼠被随机分为ZDF、taVNS、Px + taVNS和Lu + Px + taVNS组（Px：松果体切除术，Lu：鲁辛朵）。ZL大鼠作为对照组，与未参与taVNS干预的ZDF大鼠进行比较。taVNS、Px + taVNS和Lu + Px + taVNS组在麻醉下每天进行一次30分钟的taVNS干预（2/15 Hz，2 mA，30分钟/天），连续3周。每周测量所有大鼠的体重和空腹血糖（FBG），并在taVNS干预前、干预期间和干预后对ZL和ZDF组进行实时血糖检测。实验结束时测量血浆MLT浓度以及十二指肠、空肠和回肠中MRs的表达。
与ZL组相比，ZDF大鼠的FBG水平和体重增加（均P < 0.01），血浆MLT分泌以及十二指肠、空肠和回肠中MRs的表达明显降低（均P < 0.05）。在Px + taVNS组中，taVNS可通过调节非松果体来源的MLT和MRs系统显著逆转高血糖。与ZDF组相比，taVNS组中不同肠道MRs的表达增加且排列更紧密（均P < 0.05），血浆MLT分泌水平上调（P < 0.01），FBG和体重降低（均P < 0.01）。同时，在Px + taVNS组大鼠进行taVNS干预后，与taVNS组相比，我们观察到MLT分泌增加和肠道MRs数量增加（均P > 0.05）。相比之下，通过taVNS干预切除松果体并注射MRs拮抗剂鲁辛朵的ZDF大鼠未显示出这些变化。
taVNS的降糖作用可能与调节MLT水平和肠道MRs表达有关。
