Frontiers in Endocrinology (Jun 2021)

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

  • 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

DOI
https://doi.org/10.3389/fendo.2021.660793
Journal volume & issue
Vol. 12

Abstract

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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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