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Electrical stimulation of renal nerves for modulating urine glucose excretion in rats.

ABSTRACT: Background:The role of the kidney in glucose homeostasis has gained global interest. Kidneys are innervated by renal nerves, and renal denervation animal models have shown improved glucose regulation. We hypothesized that stimulation of renal nerves at kilohertz frequencies, which can block propagation of action potentials, would increase urine glucose excretion. Conversely, we hypothesized that low frequency stimulation, which has been shown to increase renal nerve activity, would decrease urine glucose excretion. Methods:We performed non-survival experiments on male rats under thiobutabarbital anesthesia. A cuff electrode was placed around the left renal artery, encircling the renal nerves. Ureters were cannulated bilaterally to obtain urine samples from each kidney independently for comparison. Renal nerves were stimulated at kilohertz frequencies (1-50 kHz) or low frequencies (2-5 Hz), with intravenous administration of a glucose bolus shortly into the 25-40-min stimulation period. Urine samples were collected at 5-10-min intervals, and colorimetric assays were used to quantify glucose excretion and concentration between stimulated and non-stimulated kidneys. A Kruskal-Wallis test was performed across all stimulation frequencies (??=?0.05), followed by a post-hoc Wilcoxon rank sum test with Bonferroni correction (??=?0.005). Results:For kilohertz frequency trials, the stimulated kidney yielded a higher average total urine glucose excretion at 33 kHz (+?24.5%; n?=?9) than 1 kHz (-?5.9%; n?=?6) and 50 kHz (+?2.3%; n?=?14). In low frequency stimulation trials, 5 Hz stimulation led to a lower average total urine glucose excretion (-?40.4%; n?=?6) than 2 Hz (-?27.2%; n?=?5). The average total urine glucose excretion between 33 kHz and 5 Hz was statistically significant (p?

SUBMITTER: Jiman AA

PROVIDER: S-EPMC7098252 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Electrical stimulation of renal nerves for modulating urine glucose excretion in rats.

Jiman Ahmad A AA Chhabra Kavaljit H KH Lewis Alfor G AG Cederna Paul S PS Seeley Randy J RJ Low Malcolm J MJ Bruns Tim M TM

Bioelectronic medicine 20180529

<h4>Background</h4>The role of the kidney in glucose homeostasis has gained global interest. Kidneys are innervated by renal nerves, and renal denervation animal models have shown improved glucose regulation. We hypothesized that stimulation of renal nerves at kilohertz frequencies, which can block propagation of action potentials, would increase urine glucose excretion. Conversely, we hypothesized that low frequency stimulation, which has been shown to increase renal nerve activity, would decre ...[more]

PMID: 32232083

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Project description:Pursuit of one goal typically precludes simultaneous pursuit of another. Thus, each exclusive activity entails an "opportunity cost:" the forgone benefits from the next-best activity eschewed. The present experiment estimates, in laboratory rats, the function that maps objective opportunity costs into subjective ones. In an operant chamber, rewarding electrical brain stimulation was delivered when the cumulative time a lever had been depressed reached a criterion duration. The value of the activities forgone during this duration is the opportunity cost of the electrical reward. We determined which of four functions best describes how objective opportunity costs, expressed as the required duration of lever depression, are translated into their subjective equivalents. The simplest account is the identity function, which equates subjective and objective opportunity costs. A variant of this function called the "sigmoidal-slope function," converges on the identity function at longer durations but deviates from it at shorter durations. The sigmoidal-slope function has the form of a hockey stick. The flat "blade" denotes a range over which opportunity costs are subjectively equivalent; these durations are too short to allow substitution of more beneficial activities. The blade extends into an upward-curving portion over which costs become discriminable and finally into the straight "handle," over which objective and subjective costs match. The two remaining functions are based on hyperbolic and exponential temporal discounting, respectively. The results are best described by the sigmoidal-slope function. That this is so suggests that different principles of intertemporal choice are involved in the evaluation of time spent working for a reward or waiting for its delivery. The subjective opportunity-cost function plays a key role in the evaluation and selection of goals. An accurate description of its form and parameters is essential to successful modeling and prediction of instrumental performance and reward-related decision making.

Dataset Information

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats.

Publications

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats.

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