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Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation

OBJECTIVE—We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to est...

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Autores principales: van den Hoek, Anita M., van Heijningen, Caroline, Schröder-van der Elst, Janny P., Ouwens, D. Margriet, Havekes, Louis M., Romijn, Johannes A., Kalsbeek, Andries, Pijl, Hanno
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518481/
https://www.ncbi.nlm.nih.gov/pubmed/18544708
http://dx.doi.org/10.2337/db07-1658
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author van den Hoek, Anita M.
van Heijningen, Caroline
Schröder-van der Elst, Janny P.
Ouwens, D. Margriet
Havekes, Louis M.
Romijn, Johannes A.
Kalsbeek, Andries
Pijl, Hanno
author_facet van den Hoek, Anita M.
van Heijningen, Caroline
Schröder-van der Elst, Janny P.
Ouwens, D. Margriet
Havekes, Louis M.
Romijn, Johannes A.
Kalsbeek, Andries
Pijl, Hanno
author_sort van den Hoek, Anita M.
collection PubMed
description OBJECTIVE—We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation. RESEARCH DESIGN AND METHODS—The effects of a continuous intracerebroventricular infusion of NPY on glucose turnover were determined in rats during a hyperinsulinemic-euglycemic clamp. Either rats were sham operated, or the liver was sympathetically (hepatic sympathectomy) or parasympathetically (hepatic parasympathectomy) denervated. RESULTS—Sympathectomy or parasympathectomy did not affect the capacity of insulin to suppress EGP in intracerebroventricular vehicle–infused animals (50 ± 8 vs. 49 ± 6 vs. 55 ± 6%, in hepatic sympathectomy vs. hepatic parasympathectomy vs. sham, respectively). Intracerebroventricular infusion of NPY significantly hampered the suppression of EGP by insulin in sham-denervated animals (29 ± 9 vs. 55 ± 6% for NPY/sham vs. vehicle/sham, respectively, P = 0.038). Selective sympathetic denervation of the liver completely blocked the effect of intracerebroventricular NPY administration on insulin action to suppress EGP (NPY/hepatic sympathectomy, 57 ± 7%), whereas selective parasympathetic denervation had no effect (NPY/hepatic parasympathectomy, 29 ± 7%). CONCLUSIONS—Intracerebroventricular administration of NPY acutely induces insulin resistance of EGP via activation of sympathetic output to the liver.
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spelling pubmed-25184812009-09-01 Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation van den Hoek, Anita M. van Heijningen, Caroline Schröder-van der Elst, Janny P. Ouwens, D. Margriet Havekes, Louis M. Romijn, Johannes A. Kalsbeek, Andries Pijl, Hanno Diabetes Metabolism OBJECTIVE—We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation. RESEARCH DESIGN AND METHODS—The effects of a continuous intracerebroventricular infusion of NPY on glucose turnover were determined in rats during a hyperinsulinemic-euglycemic clamp. Either rats were sham operated, or the liver was sympathetically (hepatic sympathectomy) or parasympathetically (hepatic parasympathectomy) denervated. RESULTS—Sympathectomy or parasympathectomy did not affect the capacity of insulin to suppress EGP in intracerebroventricular vehicle–infused animals (50 ± 8 vs. 49 ± 6 vs. 55 ± 6%, in hepatic sympathectomy vs. hepatic parasympathectomy vs. sham, respectively). Intracerebroventricular infusion of NPY significantly hampered the suppression of EGP by insulin in sham-denervated animals (29 ± 9 vs. 55 ± 6% for NPY/sham vs. vehicle/sham, respectively, P = 0.038). Selective sympathetic denervation of the liver completely blocked the effect of intracerebroventricular NPY administration on insulin action to suppress EGP (NPY/hepatic sympathectomy, 57 ± 7%), whereas selective parasympathetic denervation had no effect (NPY/hepatic parasympathectomy, 29 ± 7%). CONCLUSIONS—Intracerebroventricular administration of NPY acutely induces insulin resistance of EGP via activation of sympathetic output to the liver. American Diabetes Association 2008-09 /pmc/articles/PMC2518481/ /pubmed/18544708 http://dx.doi.org/10.2337/db07-1658 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
van den Hoek, Anita M.
van Heijningen, Caroline
Schröder-van der Elst, Janny P.
Ouwens, D. Margriet
Havekes, Louis M.
Romijn, Johannes A.
Kalsbeek, Andries
Pijl, Hanno
Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title_full Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title_fullStr Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title_full_unstemmed Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title_short Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation
title_sort intracerebroventricular administration of neuropeptide y induces hepatic insulin resistance via sympathetic innervation
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518481/
https://www.ncbi.nlm.nih.gov/pubmed/18544708
http://dx.doi.org/10.2337/db07-1658
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