Cervical vagal nerve stimulation (VNS) has been studied in the context of several conditions including epilepsy and depression. However, its effects on glucose metabolism, and its potentially beneficial effects in type II diabetes, have not yet been evaluated in humans. Efferent parasympathetic activation reduces hepatic glucose release and increases pancreatic insulin secretion, while afferent parasympathetic activation may increase hepatic glucose release and inhibit insulin secretion potentially through sympathetic activation. Thus, the effect of combined afferent and efferent cervical VNS is difficult to predict. We hypothesized that selective efferent VNS would decrease blood glucose concentration [Glu] and that selective afferent VNS would increase [Glu].
To investigate these potentially contrasting effects of efferent vs. afferent parasympathetic signaling, we recorded [Glu] and serum insulin and glucagon levels before and during 120 min of VNS in anesthetized rats. The nerve was left intact for combined afferent and efferent VNS (n=9) or sectioned proximal or distal from the stimulation electrode for selective efferent (n=8) of afferent (n=7) VNS, respectively.
We found that afferent VNS caused a strong and sustained increase in [Glu] (+108.9±20.9% or +77.6±15.4% after 120 min of combined afferent and efferent VNS or selective afferent VNS) that was not accompanied by an increase in serum insulin concentration. Combined afferent and efferent VNS significantly increased serum glucagon concentration (57.6±23.4% at 120 min of VNS), while selective afferent VNS did not increase glucagon levels. Conversely, selective efferent VNS increased [Glu] only temporarily (+28.8±11.7% at 30 min of VNS). This response coincided with a transient increase in serum glucagon concentration at 30 min of VNS (31.6±8.3%) and a strong and sustained increase in serum insulin concentration (+71.2±27.0% after 120 min of VNS).
These findings demonstrate that afferent VNS may increase [Glu] by suppressing pancreatic insulin release, while efferent VNS transiently increases [Glu] by stimulating glucagon secretion before reducing levels to or below baseline values by stimulating the release of insulin. Thus, selective efferent VNS may be potentially effective in the treatment of type II diabetes.