Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation

Abstract

Parasympathetic activation reduces hepatic glucose release and increases pancreatic insulin secretion in hyperglycemic conditions. Thus, vagal nerve stimulation (VNS) may potentially be effective in treating type II diabetes. To investigate this possibility, we hypothesized that VNS reduces blood glucose concentration [Glu] via insulin secretion. [Glu] together with insulin and glucagon serum concentrations were determined in anesthetized rats during baseline conditions and 120 min of cervical VNS with the nerve left intact for combined afferent and efferent VNS (n = 9) or the nerve sectioned proximal or distal from the stimulation electrode for selective efferent (n = 8) or afferent (n = 7) VNS, respectively. 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. However, serum insulin levels increased significantly with selective efferent VNS (+71.2 ± 27.0% after 120 min of VNS) that increased [Glu] only temporarily (+28.8 ± 11.7% at 30 min of VNS). Efferent VNS initially increased serum glucagon concentration which remained elevated for 120 min when efferent VNS was combined with afferent VNS, but returned to baseline with selective efferent VNS. These findings demonstrate that afferent VNS causes a marked and sustained increase in [Glu] that is partly mediated by suppression of pancreatic insulin secretion. In contrast, efferent VNS stimulates pancreatic glucagon secretion that appears to be antagonized by insulin secretion in the case of selective efferent VNS. Selective efferent VNS may potentially be effective in treating type II diabetes.

Cervical vagal nerve stimulation impairs glucose tolerance and suppresses insulin release in conscious rats

“…However, in a previous study (Meyers et al. ), we demonstrated that afferent signaling evoked by cervical VNS inhibits insulin secretion and markedly increases resting blood glucose levels in anesthetized rats, raising the question if patients treated with cervical VNS are at risk of developing glucose intolerance. Specifically, selective afferent cervical VNS (achieved by stimulating the cranial end of the sectioned cervical vagus nerve) caused a marked and sustained increase in blood glucose levels without concomitant increase in insulin serum concentration.…”

“…Our previous study (Meyers et al. ) demonstrated that selective afferent cervical VNS evokes a marked and sustained increase in blood glucose concentration in anesthetized rats without concomitant increase in insulin serum concentration. In contrast, selective efferent cervical VNS did not suppress insulin release and, thus increased blood glucose levels only temporarily.…”

“…; Meyers et al. ), the question if non‐selective (combined efferent and afferent) VNS at the site of the cervical vagus nerve may deteriorate glucose tolerance and place patients at risk for type 2 diabetes is highly relevant and important because our previous study demonstrated inhibition of insulin release despite marked increases in blood glucose levels during non‐selective (intact nerve) and selective afferent (dissected nerve) cervical VNS. To further explore this question, we hypothesized that chronic cervical VNS of the intact vagus nerve inhibits glucose‐induced insulin release and, thus, impairs glucose tolerance in conscious rats.…”

“…Sectioning the vagus nerve to achieve selective afferent or efferent VNS required us to perform our previous study (Meyers et al. ) during anesthesia. Anesthesia can potentially inhibit insulin release (Desborough et al.…”

Differential hemodynamic and respiratory responses to right and left cervical vagal nerve stimulation in rats

“…; Meyers et al. ). While larger animal models may have advantages over rats with regard to translational potential and more genetically engineered mouse models than rat models are available, acute and chronic vagal nerve stimulation studies are technically more feasible in rats than in mice and vagal nerve stimulation studies in rats may serve as “proof of concept” studies before designing more costly and more elaborate studies in larger animals, such as dogs, sheep, pigs, or non‐human primates.…”