Document Type

Thesis

Date of Degree

Spring 2016

Degree Name

MS (Master of Science)

Degree In

Integrative Physiology

First Advisor

Harald M. Stauss

Abstract

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.

Public Abstract

Glucose uptake into the cells is impaired in type II diabetes, leading to elevated blood glucose levels. The hormone insulin lowers blood glucose levels by increasing cellular glucose uptake. The hormone glucagon increases blood glucose levels through increased glucose release from the liver. Nerves in the body send signals about glucose homeostasis from the peripheral organs to the brain, where these signals are processed and then returned to peripheral organs to maintain glucose homeostasis. We investigated the potentially differential effects of selectively activating nerve fibers traveling from the peripheral organs to the brain vs. nerve fibers traveling from the brain to the peripheral organs on glucose homeostasis. Therefore, we electrically stimulated either the central or peripheral end of the cut vagus nerve in anesthetized rats and measured glucose, insulin, and glucagon blood concentrations.

Stimulating fibers running from the periphery to the brain strongly increased blood glucose concentration. Interestingly, this was not associated with an increase in insulin that would normally be seen when glucose levels increase, suggesting that insulin secretion is suppressed in this condition. Stimulating fibers traveling from the brain to the periphery transiently increased blood glucose concentration before returning to or below baseline levels. This response was associated with a strong increase in insulin secretion. These findings are important because they may potentially lead to novel treatment strategies for type II diabetes based on electrical stimulation of nerve fibers traveling in the vagus nerve from the brain to the periphery.

Keywords

publicabstract, Blood Pressure, Heart Rate

Pages

viii, 30

Bibliography

26-30

Copyright

Copyright 2016 Erin Elizabeth Meyers

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