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Intracerebroventricular Catalase Reduces Hepatic Insulin Sensitivity and Increases Responses to Hypoglycemia in Rats

Markkula, SP, Lyons, D, Yueh, C-Y, Riches, C, Hurst, P, Fielding, Barbara, Heisler, LK and Evans, ML (2016) Intracerebroventricular Catalase Reduces Hepatic Insulin Sensitivity and Increases Responses to Hypoglycemia in Rats Endocrinology, 157 (12). pp. 4669-4676.

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Abstract

Specialized metabolic-sensors in the hypothalamus regulate blood glucose levels by influencing hepatic glucose output and hypoglycemic counter regulatory responses. Hypothalamic reactive oxygen species (ROS) may act as a metabolic signal mediating responses to changes in glucose, other substrates and hormones. The role of ROS in the brain’s control of glucose homeostasis remains unclear. We hypothesized that hydrogen peroxide (H2O2), a relatively stable form of ROS, acts as a sensor of neuronal glucose consumption and availability and that lowering brain H2O2 with the enzyme catalase would lead to systemic responses increasing blood glucose. During hyperinsulinemic euglycemic clamps in rats, ICV catalase infusion resulted in increased hepatic glucose output, which was associated with reduced neuronal activity in the arcuate nucleus of the hypothalamus (ARC). Electrophysiological recordings revealed a subset of ARC neurons expressing pro-opiomelanocortin (POMC) that were inhibited by catalase and excited by H2O2. During hypoglycemic clamps, ICV catalase increased glucagon and epinephrine responses to hypoglycemia, consistent with perceived lower glucose levels. Our data suggest that H2O2 represents an important metabolic cue which, through tuning the electrical activity of key neuronal populations such as POMC neurons, may have a role in the brain’s influence of glucose homeostasis and energy balance.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Markkula, SPUNSPECIFIEDUNSPECIFIED
Lyons, DUNSPECIFIEDUNSPECIFIED
Yueh, C-YUNSPECIFIEDUNSPECIFIED
Riches, CUNSPECIFIEDUNSPECIFIED
Hurst, PUNSPECIFIEDUNSPECIFIED
Fielding, BarbaraB.Fielding@surrey.ac.ukUNSPECIFIED
Heisler, LKUNSPECIFIEDUNSPECIFIED
Evans, MLUNSPECIFIEDUNSPECIFIED
Date : 14 October 2016
Identification Number : 10.1210/en.2015-2054
Copyright Disclaimer : This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
Uncontrolled Keywords : Glucose sensing, Hypoglycemia, Counter regulation, Hypothalamus, Insulin sensitivity
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 16 Sep 2016 17:38
Last Modified : 11 Jul 2017 09:07
URI: http://epubs.surrey.ac.uk/id/eprint/812218

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