title: Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats.
abstract: OBJECTIVE
  Autonomic nervous system imbalance is associated with metabolic diseases, including diabetes. Glibenclamide is an antidiabetic drug that acts by stimulating insulin secretion from pancreatic beta cells and is widely used in the treatment of type 2 diabetes. Since there is scarce data concerning autonomic nervous system activity and diabetes, the aim of this work was to test whether glibenclamide can improve autonomic nervous system activity and muscarinic acetylcholine receptor function in pre-diabetic obese male rats.
  
  
  METHODS
  Pre-diabetes was induced by treatment with monosodium L-glutamate in neonatal rats. The monosodium L-glutamate group was treated with glibenclamide (2 mg/kg body weight /day) from weaning to 100 days of age, and the control group was treated with water. Body weight, food intake, Lee index, fasting glucose, insulin levels, homeostasis model assessment of insulin resistance, omeostasis model assessment of β-cell function, and fat tissue accumulation were measured. The vagus and sympathetic nerve electrical activity were recorded. Insulin secretion was measured in isolated islets challenged with glucose, acetylcholine, and the selective muscarinic acetylcholine receptor antagonists by radioimmunoassay technique.
  
  
  RESULTS
  Glibenclamide treatment prevented the onset of obesity and diminished the retroperitoneal (18%) and epididymal (25%) fat pad tissues. In addition, the glibenclamide treatment also reduced the parasympathetic activity by 28% and glycemia by 20% in monosodium L-glutamate-treated rats. The insulinotropic effect and unaltered cholinergic actions in islets from monosodium L-glutamate groups were increased.
  
  
  CONCLUSIONS
  Early glibenclamide treatment prevents monosodium L-glutamate-induced obesity onset by balancing autonomic nervous system activity.
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil. clauconationi@gmail.com.
authors.forename: Claudinéia C S
authors.initials: CCS
authors.lastname: Franco
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Kelly V
authors.initials: KV
authors.lastname: Prates
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Carina
authors.initials: C
authors.lastname: Previate
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Ana M P
authors.initials: AMP
authors.lastname: Moraes
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Camila C I
authors.initials: CCI
authors.lastname: Matiusso
authors.affiliation: Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro/RJ, Brazil.
authors.forename: Rosiane A
authors.initials: RA
authors.lastname: Miranda
authors.affiliation: Institute of Health Sciences, Federal University of Mato Grosso, Sinop, MT, Brazil.
authors.forename: Júlio C
authors.initials: JC
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Laize P
authors.initials: LP
authors.lastname: Tófolo
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Isabela P
authors.initials: IP
authors.lastname: Martins
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Barella
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Tatiane A
authors.initials: TA
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Ananda
authors.initials: A
authors.lastname: Malta
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Audrei
authors.initials: A
authors.lastname: Pavanello
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Flávio A
authors.initials: FA
authors.lastname: Francisco
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia/GO, Brazil.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Gomes
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Vander S
authors.initials: VS
authors.lastname: Alves
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Veridiana M
authors.initials: VM
authors.lastname: Moreira
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Késia P
authors.initials: KP
authors.lastname: Rigo
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Almeida
authors.affiliation: Laboratory of Mutagenesis & Genetics, Department of Cell Biology and Genetics, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Juliane R
authors.initials: JR
authors.lastname: de Sant Anna
authors.affiliation: Laboratory of Mutagenesis & Genetics, Department of Cell Biology and Genetics, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Marialba A A C
authors.initials: MAAC
authors.lastname: Prado
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Paulo C F
authors.initials: PCF
authors.lastname: Mathias
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D011236:Prediabetic State / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012970:Sodium Glutamate; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005905:Glyburide; D012970:Sodium Glutamate
keywords: Autonomic nervous system; Glibenclamide; Hyperinsulinemia; MSG; Pre-diabetic rats