Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats
Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats
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DOI：
10.1007/s12020-017-1263-z
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发表时间：
2017-05-01
期刊：
影响因子：
3.7
通讯作者：
Mathias, Paulo C. F.
中科院分区：
文献类型：
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作者：
Franco, Claudineia C. S.;Prates, Kelly V.;Mathias, Paulo C. F.
背景/目的自主神经系统失衡与包括糖尿病在内的代谢性疾病有关。格列本脲是一种通过刺激胰腺β细胞分泌胰岛素起作用的抗糖尿病药物，广泛用于治疗2型糖尿病。由于缺乏有关自主神经系统的活动和糖尿病的数据，这项工作的目的是测试是否格列本脲可以改善自主神经系统的活动和毒蕈碱乙酰胆碱受体功能在糖尿病前期肥胖的雄性rates.Methods糖尿病前期诱导治疗与谷氨酸在新生大鼠。从断奶至100日龄，谷氨酰胺组给予格列本脲（2 mg/kg体重/天），对照组给予水。测量体重、食物摄入、Lee指数、空腹血糖、胰岛素水平、胰岛素抵抗的稳态模型评估、β细胞功能的稳态模型评估和脂肪组织蓄积。记录迷走神经和交感神经电活动。用葡萄糖、乙酰胆碱和选择性毒蕈碱型乙酰胆碱受体拮抗剂通过放射免疫测定技术测定胰岛的胰岛素分泌，结果格列本脲治疗可预防肥胖的发生，并减少腹膜后（18%）和附睾（25%）脂肪垫组织。此外，格列本脲治疗还降低了28%的副交感神经活动和20%的谷氨酸盐治疗大鼠的交感神经活动。促胰岛素作用和不变的胆碱能作用在胰岛从谷氨酸组increased. Conclusionearly格列本脲治疗防止谷氨酸诱导的肥胖发作，通过平衡自主神经系统的活动。
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 beta-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.