Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats

Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal tre...

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Main Authors: Claudinéia Conationi da Silva Franco, Carina Previate, Amanda Bianchi Trombini, Rosiane Aparecida Miranda, Luiz Felipe Barella, Lucas Paulo Jacinto Saavedra, Júlio Cezar de Oliveira, Kelly Valério Prates, Laize Peron Tófolo, Tatiane Aparecida Ribeiro, Audrei Pavanello, Ananda Malta, Isabela Peixoto Martins, Veridiana Motta Moreira, Camila Cristina Ianoni Matiusso, Flávio Andrade Francisco, Vander Silva Alves, Ana Maria Praxedes de Moraes, Juliane Rocha de Sant Anna, Marialba Avezum Alves de Castro Prado, Rodrigo Mello Gomes, Elaine Vieira, Paulo Cezar de Freitas Mathias
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.660793/full
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author Claudinéia Conationi da Silva Franco
Carina Previate
Amanda Bianchi Trombini
Rosiane Aparecida Miranda
Luiz Felipe Barella
Lucas Paulo Jacinto Saavedra
Júlio Cezar de Oliveira
Kelly Valério Prates
Laize Peron Tófolo
Tatiane Aparecida Ribeiro
Audrei Pavanello
Ananda Malta
Isabela Peixoto Martins
Veridiana Motta Moreira
Camila Cristina Ianoni Matiusso
Flávio Andrade Francisco
Vander Silva Alves
Ana Maria Praxedes de Moraes
Juliane Rocha de Sant Anna
Marialba Avezum Alves de Castro Prado
Rodrigo Mello Gomes
Elaine Vieira
Paulo Cezar de Freitas Mathias
author_facet Claudinéia Conationi da Silva Franco
Carina Previate
Amanda Bianchi Trombini
Rosiane Aparecida Miranda
Luiz Felipe Barella
Lucas Paulo Jacinto Saavedra
Júlio Cezar de Oliveira
Kelly Valério Prates
Laize Peron Tófolo
Tatiane Aparecida Ribeiro
Audrei Pavanello
Ananda Malta
Isabela Peixoto Martins
Veridiana Motta Moreira
Camila Cristina Ianoni Matiusso
Flávio Andrade Francisco
Vander Silva Alves
Ana Maria Praxedes de Moraes
Juliane Rocha de Sant Anna
Marialba Avezum Alves de Castro Prado
Rodrigo Mello Gomes
Elaine Vieira
Paulo Cezar de Freitas Mathias
author_sort Claudinéia Conationi da Silva Franco
collection DOAJ
description Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21–100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.
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spelling doaj.art-21afd311be054c70abafe78c2c55e65c2022-12-21T20:04:32ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-06-011210.3389/fendo.2021.660793660793Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated RatsClaudinéia Conationi da Silva Franco0Carina Previate1Amanda Bianchi Trombini2Rosiane Aparecida Miranda3Luiz Felipe Barella4Lucas Paulo Jacinto Saavedra5Júlio Cezar de Oliveira6Kelly Valério Prates7Laize Peron Tófolo8Tatiane Aparecida Ribeiro9Audrei Pavanello10Ananda Malta11Isabela Peixoto Martins12Veridiana Motta Moreira13Camila Cristina Ianoni Matiusso14Flávio Andrade Francisco15Vander Silva Alves16Ana Maria Praxedes de Moraes17Juliane Rocha de Sant Anna18Marialba Avezum Alves de Castro Prado19Rodrigo Mello Gomes20Elaine Vieira21Paulo Cezar de Freitas Mathias22Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilCarlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilInstitute of Health Sciences, Federal University of Mato Grosso-Sinop, Sinop, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilLaboratory of Mutagenesis & Genetics, Department of Cell Biology and Genetics, State University of Maringá, Maringá, BrazilLaboratory of Mutagenesis & Genetics, Department of Cell Biology and Genetics, State University of Maringá, Maringá, BrazilDepartment of Physiological Sciences, Federal University of Goiás, Goiânia, BrazilPostgraduate Program on Physical Education, University Católica of Brasília, Brasília, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, BrazilMetformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21–100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.https://www.frontiersin.org/articles/10.3389/fendo.2021.660793/fullmetformininsulin secretionacetylcholineautonomic nervous systemMSG-obese rats
spellingShingle Claudinéia Conationi da Silva Franco
Carina Previate
Amanda Bianchi Trombini
Rosiane Aparecida Miranda
Luiz Felipe Barella
Lucas Paulo Jacinto Saavedra
Júlio Cezar de Oliveira
Kelly Valério Prates
Laize Peron Tófolo
Tatiane Aparecida Ribeiro
Audrei Pavanello
Ananda Malta
Isabela Peixoto Martins
Veridiana Motta Moreira
Camila Cristina Ianoni Matiusso
Flávio Andrade Francisco
Vander Silva Alves
Ana Maria Praxedes de Moraes
Juliane Rocha de Sant Anna
Marialba Avezum Alves de Castro Prado
Rodrigo Mello Gomes
Elaine Vieira
Paulo Cezar de Freitas Mathias
Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
Frontiers in Endocrinology
metformin
insulin secretion
acetylcholine
autonomic nervous system
MSG-obese rats
title Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
title_full Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
title_fullStr Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
title_full_unstemmed Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
title_short Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats
title_sort metformin improves autonomic nervous system imbalance and metabolic dysfunction in monosodium l glutamate treated rats
topic metformin
insulin secretion
acetylcholine
autonomic nervous system
MSG-obese rats
url https://www.frontiersin.org/articles/10.3389/fendo.2021.660793/full
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