How Do the Brain Neural Networks Involved in Glucose Homeostasis Affect Cardiovascular Function Through Metabolic Dysregulation?

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 4256

Special Issue Editors


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Guest Editor
Heart Research Institute, The University of Sydney, 7 Eliza St, Newtown, NSW 2042, Australia
Interests: autonomic neuroscience; cardiometabolic; neuropeptides; diabetes

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Guest Editor
Department of Pharmacology, Physiology & Neuroscience, Medical Science Building (MSB), 185 South Orange Avenue, Room I 681, Newark, NJ 07101, USA
Interests: metabolism; glucose metabolism; insulin signaling; reactive oxygen species; neuroendocrinology; metabolic diseases
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Special Issue Information

Dear Colleagues,

Glucose dysregulation contributes to the development of cardiovascular disease through the emergence of metabolic disorders such as obesity, diabetes, and metabolic syndrome, which are becoming increasingly prevalent. The brain, specifically the brainstem and hypothalamus, contains neural networks that regulate glucose homeostasis and play a crucial role in metabolism and cardiovascular function. The aim of this Special Issue of Metabolites is to examine the intricate relationship between glucose homeostasis and cardiovascular function within the context of brain neural networks and metabolic dysregulation. The scope of the issue includes, but is not limited to, research on how changes in brain glucose-regulating pathways affect the activity of the sympathetic and parasympathetic nervous systems, the release of hormones and neurotransmitters, inflammation, oxidative stress, appetite, satiety, and energy metabolism in relation to cardiovascular function in both health and disease.

The purpose of this Special Issue is to present a collection of original research articles and reviews toward enabling a comprehensive understanding of the main theme.

Dr. Polina Nedoboy
Prof. Dr. Vanessa Routh
Guest Editors

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Keywords

  • cardiovascular function
  • autonomic nervous system
  • neurotransmitters
  • hypothalamus
  • brainstem
  • glucose sensing
  • metabolic dysregulation
  • metabolome

Published Papers (2 papers)

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Review

28 pages, 1944 KiB  
Review
Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure—A Diabetic Perspective
by Manjula Senthilkumaran, Coen Koch, Mauritz Frederick Herselman and Larisa Bobrovskaya
Metabolites 2024, 14(2), 100; https://doi.org/10.3390/metabo14020100 - 31 Jan 2024
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Abstract
Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single [...] Read more.
Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge. Full article
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17 pages, 1791 KiB  
Review
Brain Regulation of Cardiac Function during Hypoglycemia
by Matthew E. Chambers, Emily H. Nuibe and Candace M. Reno-Bernstein
Metabolites 2023, 13(10), 1089; https://doi.org/10.3390/metabo13101089 - 18 Oct 2023
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Abstract
Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this [...] Read more.
Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this fall in glucose. The autonomic nervous system innervates the heart, and during hypoglycemia, can cause many changes. Clinical and animal studies have revealed changes in electrocardiograms during hypoglycemia. Cardiac repolarization defects (QTc prolongation) occur during moderate levels of hypoglycemia. When hypoglycemia is severe, it can be fatal. Cardiac arrhythmias are thought to be the major mediator of sudden death due to severe hypoglycemia. Both the sympathetic and parasympathetic nervous systems of the brain have been implicated in regulating these arrhythmias. Besides cardiac arrhythmias, hypoglycemia can have profound changes in the heart and most of these changes are exacerbated in the setting of diabetes. A better understanding of how the brain regulates cardiac changes during hypoglycemia will allow for better therapeutic intervention to prevent cardiovascular death associated with hypoglycemia in people with diabetes. The aim of this paper is to provide a narrative review of what is known in the field regarding how the brain regulates the heart during hypoglycemia. Full article
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