Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Objective: Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes mode...

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Main Authors: Sofiya Gancheva, Alessandra Bierwagen, Daniel F. Markgraf, Gidon J. Bönhof, Kevin G. Murphy, Erifili Hatziagelaki, Jesper Lundbom, Dan Ziegler, Michael Roden
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Molecular Metabolism
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877817305380
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author Sofiya Gancheva
Alessandra Bierwagen
Daniel F. Markgraf
Gidon J. Bönhof
Kevin G. Murphy
Erifili Hatziagelaki
Jesper Lundbom
Dan Ziegler
Michael Roden
author_facet Sofiya Gancheva
Alessandra Bierwagen
Daniel F. Markgraf
Gidon J. Bönhof
Kevin G. Murphy
Erifili Hatziagelaki
Jesper Lundbom
Dan Ziegler
Michael Roden
author_sort Sofiya Gancheva
collection DOAJ
description Objective: Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2). Methods: Heart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation. Results: taVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected. Conclusion: Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans. Author Video: Author Video Watch what authors say about their articles Keywords: Vagus nerve stimulation, Hepatic insulin sensitivity, Hepatic energy metabolism, Liver fat content
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spelling doaj.art-9fc64979be264e8dbd49ecdcf0616c922022-12-22T02:16:19ZengElsevierMolecular Metabolism2212-87782018-01-0177179Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolismSofiya Gancheva0Alessandra Bierwagen1Daniel F. Markgraf2Gidon J. Bönhof3Kevin G. Murphy4Erifili Hatziagelaki5Jesper Lundbom6Dan Ziegler7Michael Roden8Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, GermanySection of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College Healthcare NHS Trust, London, United Kingdom2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, “Attikon” University General Hospital, Athens, GreeceInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, GermanyInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; German Center of Diabetes Research (DZD e.V.), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Corresponding author. Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, c/o Auf‘m Hennekamp 65, 40225 Düsseldorf, Germany. Fax: +49 211 3382 691.Objective: Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2). Methods: Heart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation. Results: taVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected. Conclusion: Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans. Author Video: Author Video Watch what authors say about their articles Keywords: Vagus nerve stimulation, Hepatic insulin sensitivity, Hepatic energy metabolism, Liver fat contenthttp://www.sciencedirect.com/science/article/pii/S2212877817305380
spellingShingle Sofiya Gancheva
Alessandra Bierwagen
Daniel F. Markgraf
Gidon J. Bönhof
Kevin G. Murphy
Erifili Hatziagelaki
Jesper Lundbom
Dan Ziegler
Michael Roden
Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
Molecular Metabolism
title Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
title_full Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
title_fullStr Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
title_full_unstemmed Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
title_short Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism
title_sort constant hepatic atp concentrations during prolonged fasting and absence of effects of cerbomed nemos r on parasympathetic tone and hepatic energy metabolism
url http://www.sciencedirect.com/science/article/pii/S2212877817305380
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