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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Autonomic Neuroscience
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1471387
This article is part of the Research Topic New applications of non-invasive vagal stimulation to modulate disease progression View all articles

Transcutaneous auricular vagal nerve stimulation modulates blood glucose in ZDF rats via intestinal melatonin receptors and melatonin secretion

Provisionally accepted
Yuzhengheng Zhang Yuzhengheng Zhang 1Ningyi Zou Ningyi Zou 1Chen Xin Chen Xin 1Yifei Wang Yifei Wang 1Zixuan Zhang Zixuan Zhang 1Peijing Rong Peijing Rong 2*Shaoyuan Li Shaoyuan Li 1*
  • 1 Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China
  • 2 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China

The final, formatted version of the article will be published soon.

    Background: 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.Methods: Adult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. 40 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. 30 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.Results: Compared with the ZL group, the level of FBG and body weight increased (all P < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all P < 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 P < 0.05), the level of plasma MLT secretion was up-regulated (P < 0.01), and FBG and body weight were decreased (both P < 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 P > 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.

    Keywords: Transcutaneous auricular vagus nerve stimulation, Melatonin, intestinal melatonin receptors, Hypoglycemic effect, Vagus Nerve

    Received: 27 Jul 2024; Accepted: 18 Oct 2024.

    Copyright: © 2024 Zhang, Zou, Xin, Wang, Zhang, Rong and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Peijing Rong, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
    Shaoyuan Li, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China

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