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

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.