Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model
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...
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15257 |
| _version_ | 1828402690284060672 |
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| author | Sophie C. Payne Glenn Ward James B. Fallon Tomoko Hyakumura Johannes B. Prins Sofianos Andrikopoulos Richard J. MacIsaac Joel Villalobos |
| author_facet | Sophie C. Payne Glenn Ward James B. Fallon Tomoko Hyakumura Johannes B. Prins Sofianos Andrikopoulos Richard J. MacIsaac Joel Villalobos |
| author_sort | Sophie C. Payne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T10:05:07Z |
| format | Article |
| id | doaj.art-12c3de092b0f4fc5bf5b868985542b7d |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-10T10:05:07Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-12c3de092b0f4fc5bf5b868985542b7d2022-12-22T01:53:16ZengWileyPhysiological Reports2051-817X2022-04-01108n/an/a10.14814/phy2.15257Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat modelSophie C. Payne0Glenn Ward1James B. Fallon2Tomoko Hyakumura3Johannes B. Prins4Sofianos Andrikopoulos5Richard J. MacIsaac6Joel Villalobos7Bionics Institute East Melbourne Victoria AustraliaBionics Institute East Melbourne Victoria AustraliaBionics Institute East Melbourne Victoria AustraliaBionics Institute East Melbourne Victoria AustraliaMelbourne Medical School University of Melbourne Parkville Victoria AustraliaAustralian Centre for Accelerating Diabetes Innovations University of Melbourne Melbourne AustraliaBionics Institute East Melbourne Victoria AustraliaBionics Institute East Melbourne Victoria AustraliaAbstract 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.https://doi.org/10.14814/phy2.15257autonomic nervous systembioelectric medicinedirectional stimulationmedical devicesmetabolic diseaseselective peripheral nerve stimulation |
| spellingShingle | Sophie C. Payne Glenn Ward James B. Fallon Tomoko Hyakumura Johannes B. Prins Sofianos Andrikopoulos Richard J. MacIsaac Joel Villalobos Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model Physiological Reports autonomic nervous system bioelectric medicine directional stimulation medical devices metabolic disease selective peripheral nerve stimulation |
| title | Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| title_full | Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| title_fullStr | Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| title_full_unstemmed | Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| title_short | Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| title_sort | blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model |
| topic | autonomic nervous system bioelectric medicine directional stimulation medical devices metabolic disease selective peripheral nerve stimulation |
| url | https://doi.org/10.14814/phy2.15257 |
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