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Vagal Nerve Stimulation for Glycemic Control in a Rodent Model of Type 2 Diabetes

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Abstract

Background

Vagal nerve stimulation (VNS) has been reported to reduce body weight and improve sympathovagal imbalance in both basic and clinical studies. Its effects on glycemic control were however unclear. The aims of this study were to investigate the effects of VNS with various parameters on blood glucose and its possible mechanisms in rats.

Methods

A hyperglycemic rodent model induced by glucagon was used initially to optimize the VNS parameters; then, a type 2 diabetic rodent model induced by high-fat diet combined with streptozotocin was used to validate the VNS method. The VNS electrodes were implanted at the dorsal subdiaphragmatic vagus; three subcutaneous electrodes were implanted at the chest area for recording electrocardiogram in rats induced by glucagon.

Results

(1) VNS with short pulse width of 0.3 ms but not 3 ms reduced blood glucose during an oral glucose tolerance test (OGTT), with a 38.4% reduction at 15 min and 26.9% at 30 min (P < 0.05, vs. sham-VNS respectively). (2) VNS at low frequency of 5 Hz but not 14 Hz or 40 Hz reduced blood glucose during the OGTT (P < 0.05, vs. sham-VNS). (3) Intermittent VNS was more potent than continuous VNS (P < 0.01). (4) No difference was found between unilateral VNS and bilateral VNS. (5) VNS enhanced vagal activity (P = 0.005). (6) The hypoglycemic effect of VNS was blocked by glucagon-like peptide-1 (GLP-1) antagonist exendin-4.

Conclusions

VNS at 5 Hz reduces blood glucose in diabetic rats by enhancing vagal efferent activity and the release of GLP-1.

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Funding

Jieyun Yin was partially supported by a grant from NIH-SPARC (Stimulating Peripheral Activity for Relieving Conditions) (1U18TR001926).

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Author notes

  1. Jieyun Yin and Feng Ji contributed equally to this work.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA

    Jieyun Yin, Feng Ji, Payam Gharibani & Jiande DZ Chen

  2. Transtimulation Research, Inc, Oklahoma City, OK, USA

    Jieyun Yin

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  1. Jieyun Yin
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Correspondence to Jieyun Yin.

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Yin, J., Ji, F., Gharibani, P. et al. Vagal Nerve Stimulation for Glycemic Control in a Rodent Model of Type 2 Diabetes. OBES SURG 29, 2869–2877 (2019). https://doi.org/10.1007/s11695-019-03901-9

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