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Title: Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model.
Austin Authors: Payne, Sophie C;Ward, Glenn;Fallon, James B;Hyakumura, Tomoko;Prins, Johannes B;Andrikopoulos, Sofianos;MacIsaac, Richard J;Villalobos, Joel
Affiliation: Medicine (University of Melbourne)
Department of Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Melbourne, Australia
Bionics Institute, East Melbourne, Victoria, Australia
Department of Medical Bionics, University of Melbourne, Parkville, Victoria, Australia
Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia
Issue Date: Apr-2022
Publication information: Physiological Reports 2022; 10(8): e15257
Abstract: Vagus nerve stimulation is emerging as a promising treatment for type 2 diabetes. Here, we evaluated the ability of stimulation of the vagus nerve to reduce glycemia in awake, freely moving metabolically compromised rats. A model of type 2 diabetes (n = 10) was induced using a high-fat diet and low doses of streptozotocin. Stimulation of the abdominal vagus nerve was achieved by pairing 15 Hz pulses on a distal pair of electrodes with high-frequency blocking stimulation (26 kHz, 4 mA) on a proximal pair of electrodes to preferentially produce efferent conducting activity (eVNS). Stimulation was well tolerated in awake, freely moving rats. During 1 h of eVNS, glycemia decreased in 90% of subjects (-1.25 ± 1.25 mM h, p = 0.017), and 2 dB above neural threshold was established as the most effective "dose" of eVNS (p = 0.009). Following 5 weeks of implantation, eVNS was still effective, resulting in significantly decreased glycemia (-1.7 ± 0.6 mM h, p = 0.003) during 1 h of eVNS. There were no overt changes in fascicle area or signs of histopathological damage observed in implanted vagal nerve tissue following chronic implantation and stimulation. Demonstration of the biocompatibility and safety of eVNS in awake, metabolically compromised animals is a critical first step to establishing this therapy for clinical use. With further development, eVNS could be a promising novel therapy for treating type 2 diabetes.
DOI: 10.14814/phy2.15257
ORCID: 0000-0002-3428-2275
Journal: Physiological Reports
PubMed URL: 35439355
PubMed URL:
Type: Journal Article
Subjects: autonomic nervous system
bioelectric medicine
directional stimulation
medical devices
metabolic disease
selective peripheral nerve stimulation
Appears in Collections:Journal articles

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