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Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model

Citation

Payne, Sophie et al. (2022), Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model, Dryad, Dataset, https://doi.org/10.5061/dryad.cjsxksn72

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 glycaemia 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 hour of eVNS, glycaemia 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 glycaemia (-1.7±0.6 mM·h, P=0.003) during 1 hour 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 biocompatability 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.

Methods

See https://doi.org/10.14814/phy2.15257

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 glycaemia 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 hour of eVNS, glycaemia 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 glycaemia (-1.7±0.6 mM·h, P=0.003) during 1 hour 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 biocompatability 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.

Funding

Bionics Institute Incubation Fund, Award: PINT013

St. Vincent’s Research Endowment Fund, Award: 85257

Cass Foundation Limited, Award: 8511

University of Melbourne’s Early Career Researcher Grants Scheme, Award: 1757246

State Government of Victoria