Stimulating the vagus nerve can reduce blood glucose levels

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image of vagus nerve implant device

Researchers attached this electrode array to the vagus nerve in the abdomen.

An inability to control blood glucose levels is a hallmark of type 2 diabetes. Many people with this disorder can’t control their blood glucose using drugs alone, so new therapies are needed.

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By stimulating the vagus nerve using implantable electrodes, University of Melbourne researchers have safely reduced blood glucose levels in an animal model.

The vagus nerve runs from the brain to the abdomen and has a range of functions. It is involved in the gag reflex, in maintaining heart rate, and in controlling gut muscles. It also has roles in glucose metabolism and insulin secretion – the dysfunction of which causes type 2 diabetes.

Vagus nerve stimulation is used to treat clinical depression and epilepsy and is being tested as a treatment for rheumatoid arthritis and inflammatory bowel disease. Studies have shown that it might also be useful in controlling blood sugar levels. However, how the vagus nerve’s activity could be modulated to achieve the desired levels was not clear.

To answer this question, researchers conducted experiments in an animal model of type 2 diabetes. The research was led by Dr Sophie Payne from the Department of Medical Bionics and the Bionics Institute and involved researchers from the Melbourne Medical School and the Australian Centre for Accelerating Diabetes Innovations.

The researchers attached an electrode array to the vagus nerve in the abdomen. The array included three pairs of electrodes. One pair was used to activate the vagus nerve. Another pair was used to block this activity from travelling back to the brain, where it could have unintended effects. The last pair of electrodes was used to record the activity of the nerve in response to stimulation.

One week after implantation, the researchers gave the animals excess sugar to increase their blood glucose levels. Then they applied nerve stimulation and blocking for one hour while continuously measuring blood glucose. They repeated this approach every few days for three weeks.

The combination of nerve activation and blocking reduced blood glucose levels by up to 72 per cent. This effect was observed at both the beginning and the end of the experiment, which suggests that the animals tolerated the implanted electrodes. The researchers confirmed that the implanted electrodes caused no damage to tissue.

Next steps

The researchers are now trying to determine precisely how vagus nerve stimulation reduces blood glucose levels. They are also comparing it to standard drug treatments. In parallel, researchers at the Bionics Institute are developing a device that can deliver the required stimulation for use in a first-in-human clinical trial.

Publication

Payne SC et al (2022) Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model. Physiological Reports 10: e15257. doi: 10.14814/phy2.15257

Image credit: Bionics Institute

Funding

Bionics Institute Incubation Fund

St Vincent's Hospital Melbourne Research Endowment Fund (85257)

The CASS Foundation (8511)

The University of Melbourne Early Career Researcher Grant (1757246)

Victorian Government Operational Infrastructure Support Program

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