Abstract
Despite advancements in pharmacotherapies, glycemia is poorly controlled in type 2 diabetic patients. As the vagus nerve regulates energy metabolism, here we evaluated the effect various electrical vagus nerve stimulation strategies have on glycemia and glucose‐regulating hormones, as a first step to developing a novel therapy of type 2 diabetes. Sprague–Dawley rats were anesthetized, the abdominal (anterior) vagus nerve implanted, and various stimulation strategies applied to the nerve: (a) 15 Hz; (b) 4 kHz, or 40 kHz and; (c) a combination of 15 Hz and 40 kHz to directionally activate afferent or efferent vagal fibers. Following a glucose bolus (500 mg/kg, I.V.), stimulation strategies were applied (60 min) and serial blood samples taken. No stimulation was used as a crossover control sequence. Applying 15 Hz stimulation significantly increased glucose (+2.9 ± 0.2 mM·hr, p = .015) and glucagon (+17.1 ± 8.0 pg·hr/ml, p = .022), compared to no stimulation. Application of 4 kHz stimulation also significantly increased glucose levels (+1.5 ± 0.5 mM·hr, p = .049), while 40 kHz frequency stimulation resulted in no changes to glucose levels but did significantly lower glucagon (−12.3 ± 1.1 pg·hr/ml, p = .0009). Directional afferent stimulation increased glucose (+2.4 ± 1.5 mM·hr) and glucagon levels (+39.5 ± 15.0 pg·hr/ml). Despite hyperglycemia resulting when VNS, aVNS, and 4 kHz stimulation strategies were applied, the changes in insulin levels were not significant (p ≥ .05). In summary, vagus nerve stimulation modulates glycemia by effecting glucagon and insulin secretions, and high‐frequency 40 kHz stimulation may have potential application for the treatment of type 2 diabetes.
Highlights
Diabetes mellitus is a chronic, progressive condition that affects over 350 million people worldwide
The high levels of insulin secreted in compensation lead to subsequent dysfunction of β-cells in the pancreas, which eventually leads to a permanent reduction in insulin secretion (Stumvoll, Goldstein, & van Haeften, 2005)
We found that applying different electrical stimulation strategies to the abdominal
Summary
Research reported in this publication was supported by the St. Vincent's Research Endowment Fund (85257), the Cass Foundation Limited (8511), and the University of Melbourne's Early Career Researcher Grants Scheme (1757246).
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