Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats

Background/Aims 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...

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Bibliographic Details
Published in:	Endocrine Vol. 56; no. 2; pp. 346 - 356
Main Authors:	Franco, Claudinéia C. S., Prates, Kelly V., Previate, Carina, Moraes, Ana M. P., Matiusso, Camila C. I., Miranda, Rosiane A., de Oliveira, Júlio C., Tófolo, Laize P., Martins, Isabela P., Barella, Luiz F., Ribeiro, Tatiane A., Malta, Ananda, Pavanello, Audrei, Francisco, Flávio A., Gomes, Rodrigo M., Alves, Vander S., Moreira, Veridiana M., Rigo, Késia P., Almeida, Douglas L., de Sant Anna, Juliane R., Prado, Marialba A. A. C., Mathias, Paulo C. F.
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-05-2017 Springer Nature B.V
Subjects:	Adipose Tissue - drug effects Adipose Tissue - metabolism Adipose Tissue - physiopathology Animals Autonomic Nervous System - drug effects Autonomic Nervous System - metabolism Autonomic Nervous System - physiopathology Beta cells Blood glucose Blood Glucose - metabolism Body Weight - drug effects Diabetes Eating - drug effects Endocrinology Glyburide - pharmacology Glyburide - therapeutic use Humanities and Social Sciences Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Insulin - blood Insulin Resistance - physiology Insulin secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Internal Medicine Male Medicine Medicine & Public Health Metabolism multidisciplinary Obesity Obesity - metabolism Obesity - physiopathology Original Article Prediabetic State - chemically induced Prediabetic State - drug therapy Prediabetic State - metabolism Prediabetic State - physiopathology Rats Rats, Wistar Science Sodium Glutamate Vagus Nerve - drug effects Vagus Nerve - physiopathology MSG Hyperinsulinemia Pre-diabetic rats Glibenclamide Autonomic nervous system
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Summary:	Background/Aims 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. Conclusion Early glibenclamide treatment prevents monosodium L-glutamate-induced obesity onset by balancing autonomic nervous system activity.
ISSN:	1355-008X 1559-0100
DOI:	10.1007/s12020-017-1263-z