PPG neurons in the nucleus of the solitary tract modulate heart rate but do not mediate GLP-1 receptor agonist-induced tachycardia in mice.

Animals Disease Models, Animal Electrocardiography Exenatide / pharmacology Glucagon-Like Peptide-1 Receptor / agonists Heart Rate / drug effects Mice Mice, Transgenic Neurons / drug effects Proglucagon / biosynthesis Solitary Nucleus / cytology Spinal Cord / drug effects Sympathetic Nervous System / drug effects Tachycardia / diagnosis
Biotelemetry Cardiovascular function Chemogenetics GLP-1 PPG neurons Sympathetic outflow

Journal

Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730

Informations de publication

Date de publication:
09 2020
Historique:
received: 24 03 2020
revised: 13 05 2020
accepted: 13 05 2020
pubmed: 25 5 2020
medline: 9 7 2021
entrez: 25 5 2020
Statut: ppublish

Résumé

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used as anti-diabetic drugs and are approved for obesity treatment. However, GLP-1RAs also affect heart rate (HR) and arterial blood pressure (ABP) in rodents and humans. Although the activation of GLP-1 receptors (GLP-1R) is known to increase HR, the circuits recruited are unclear, and in particular, it is unknown whether GLP-1RAs activate preproglucagon (PPG) neurons, the brain source of GLP-1, to elicit these effects. We investigated the effect of GLP-1RAs on heart rate in anaesthetized adult mice. In a separate study, we manipulated the activity of nucleus tractus solitarius (NTS) PPG neurons (PPG Systemic administration of the GLP-1RA Ex-4 increased resting HR in anaesthetized or conscious mice, but had no effect on ABP in conscious mice. This effect was abolished by β-adrenoceptor blockade with atenolol, but unaffected by the muscarinic antagonist atropine. Furthermore, Ex-4-induced tachycardia persisted when PPG These results demonstrate that both systemic application of Ex-4 or GLP-1 and chemogenetic activation of PPG

Identifiants

DOI: 10.1016/j.molmet.2020.101024 PMID: 32446875 PMC: PMC7317700
pubmed: 32446875
pii: S2212-8778(20)30098-3
doi: 10.1016/j.molmet.2020.101024
pmc: PMC7317700
pii:
doi:

Substances chimiques

Glucagon-Like Peptide-1 Receptor 0
Proglucagon 55963-74-1
Exenatide 9P1872D4OL

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101024

Subventions

Organisme : Wellcome Trust
ID : 200893
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/43/30960
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200893/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N02589X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/3
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Références

Physiol Behav. 2018 Aug 1;192:17-22
pubmed: 29510158
Endocrinology. 2018 Apr 1;159(4):1570-1584
pubmed: 29444223
J Neurosci. 2003 Jul 16;23(15):6163-70
pubmed: 12867498
J Neurosci. 2019 Apr 3;39(14):2649-2663
pubmed: 30683681
Am J Physiol. 1999 Nov;277(5):E784-91
pubmed: 10567003
Endocrinology. 2009 Apr;150(4):1680-7
pubmed: 19074583
Regul Pept. 1996 Nov 14;67(1):63-8
pubmed: 8952007
Endocrinology. 2003 Jun;144(6):2242-52
pubmed: 12746281
Mol Metab. 2017 Nov;6(11):1339-1349
pubmed: 29107282
PLoS One. 2012;7(7):e39722
pubmed: 22829870
J Clin Invest. 2002 Jul;110(1):43-52
pubmed: 12093887
Mol Metab. 2017 Jun 07;6(8):909-921
pubmed: 28752054
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5913-8
pubmed: 19307579
Exp Neurol. 2008 Apr;210(2):458-66
pubmed: 18177641
Neuroscience. 2015 Jan 22;284:872-887
pubmed: 25450967
Neuroscience. 2013 Jan 15;229:130-43
pubmed: 23069752
Diabetes. 2014 Apr;63(4):1224-33
pubmed: 24296712
Diabetes. 2019 Jan;68(1):21-33
pubmed: 30279161
Nat Commun. 2020 Jan 24;11(1):467
pubmed: 31980626
Endocrinology. 2010 Jun;151(6):2629-40
pubmed: 20363879
Mol Metab. 2015 Aug 05;4(10):718-31
pubmed: 26500843
Clin Sci (Lond). 1998 Dec;95(6):719-24
pubmed: 9831697
Am J Physiol. 1994 Mar;266(3 Pt 1):E459-66
pubmed: 8166268
J Neurosci. 2015 Jul 29;35(30):10701-14
pubmed: 26224855
Nat Neurosci. 2011 Mar;14(3):297-9
pubmed: 21278730
Cardiovasc Res. 2011 Jan 1;89(1):72-8
pubmed: 20736238
Nature. 1996 Jan 4;379(6560):69-72
pubmed: 8538742
Prog Neurobiol. 2010 Nov;92(3):442-62
pubmed: 20638440
BMJ Open. 2013 Jan 24;3(1):
pubmed: 23355666
Compr Physiol. 2016 Mar 15;6(2):603-21
pubmed: 27065163
J Neurochem. 1996 Mar;66(3):920-7
pubmed: 8769850
Cogent Biol. 2016 Dec 31;2(1):1229086
pubmed: 27722184
J Clin Invest. 2014 Oct;124(10):4473-88
pubmed: 25202980
Am J Physiol Regul Integr Comp Physiol. 2016 Jul 1;311(1):R115-23
pubmed: 27097661
Int J Obes (Lond). 2006 Sep;30(9):1332-40
pubmed: 16534527
Diabetologia. 2012 Sep;55(9):2445-55
pubmed: 22638549
Physiol Rev. 2007 Oct;87(4):1409-39
pubmed: 17928588
Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R795-804
pubmed: 26290108
J Clin Invest. 2017 Mar 1;127(3):1031-1045
pubmed: 28218622
Diabetes. 1993 May;42(5):658-61
pubmed: 8482423
Nat Med. 2013 May;19(5):567-75
pubmed: 23542788
Physiol Behav. 2019 Jul 1;206:191-199
pubmed: 30980855
Front Neurosci. 2013 Jan 21;6:199
pubmed: 23346044
Cell Metab. 2008 Dec;8(6):532-9
pubmed: 19041768
Endocrinology. 2011 Aug;152(8):3103-12
pubmed: 21693680
J Comp Neurol. 1999 Jan 11;403(2):261-80
pubmed: 9886047
Diabetes. 2008 Oct;57(10):2577-87
pubmed: 18633100
Physiol Behav. 2013 Oct 2;122:201-7
pubmed: 23623992
J Neurosci. 2012 Apr 4;32(14):4812-20
pubmed: 22492036
Brain Struct Funct. 2015 Sep;220(5):3011-22
pubmed: 25012114
J Neurosci. 2019 Dec 4;39(49):9767-9781
pubmed: 31666353
Neurosci Biobehav Rev. 2017 Mar;74(Pt B):366-375
pubmed: 27208411
Diabetes. 2009 Dec;58(12):2820-7
pubmed: 19741167
Endocrinology. 2008 Aug;149(8):4059-68
pubmed: 18420740
J Clin Invest. 2011 Apr;121(4):1424-8
pubmed: 21364278
Exp Physiol. 1997 Jul;82(4):709-16
pubmed: 9257113
J Neurosci. 2017 Jan 4;37(1):184-193
pubmed: 28053040
J Neurosci. 2003 Apr 1;23(7):2939-46
pubmed: 12684481
Circ Arrhythm Electrophysiol. 2018 Oct;11(10):e006740
pubmed: 30354404
Psychophysiology. 1974 Jul;11(4):405-27
pubmed: 4854556
J Auton Nerv Syst. 1998 Aug 6;72(1):46-54
pubmed: 9760079
Am J Physiol. 1996 Oct;271(4 Pt 2):R848-56
pubmed: 8897973
Endocrinol Metab (Seoul). 2016 Jun;31(2):258-74
pubmed: 27118277
J Anesth. 1997 Mar;11(1):22-26
pubmed: 28921265
Neuroscience. 2011 Apr 28;180:111-21
pubmed: 21329743
Stress. 2015;18(4):381-99
pubmed: 26303312
Sci Rep. 2018 Jul 9;8(1):10310
pubmed: 29985439
Diabetes Care. 2016 Feb;39(2):e22-3
pubmed: 26681718
Physiol Behav. 2017 Apr 1;172:49-59
pubmed: 27793557

Auteurs

Marie K Holt (MK)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK.

Daniel R Cook (DR)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK.

Daniel I Brierley (DI)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK.

James E Richards (JE)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK.

Frank Reimann (F)

Wellcome Trust/MRC Institute of Metabolic Science (IMS), Addenbrookes Hospital, University of Cambridge, Cambridge, UK.

Alexander V Gourine (AV)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK.

Nephtali Marina (N)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK. Electronic address: n.marina@ucl.ac.uk.

Stefan Trapp (S)

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK. Electronic address: s.trapp@ucl.ac.uk.

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Électrodiagnostic › Électrocardiographie › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Venins › Exénatide › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormone gastrointestinale › Récepteurs des peptides similaires au glucagon › Récepteur du peptide-1 similaire au glucagon › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Hémodynamique › Rythme cardiaque › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Cellules › Neurones › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Précurseurs de protéines › Proglucagon › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Tronc cérébral › Rhombencéphale › Myélencéphale › Moelle allongée › Noyau du tractus solitaire › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Système nerveux › Système nerveux central › Moelle spinale › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › Système nerveux › Système nerveux périphérique › Système nerveux autonome › Système nerveux sympathique › PPG neurons in the nucleus of the solitary...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Troubles du rythme cardiaque › Tachycardie › PPG neurons in the nucleus of the solitary...