Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release
Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release
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DOI：
10.1007/s13105-016-0501-9
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发表时间：
2016-12-01
影响因子：
3.4
通讯作者：
Bonfleur, Maria Lucia
中科院分区：
文献类型：
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作者：
Balbo, Sandra Lucinei;Ribeiro, Rosane Aparecida;Bonfleur, Maria Lucia
在此，我们研究了蛛网膜下迷走神经切断术是否对咖啡厅（CAF）肥胖大鼠的肥胖、血糖稳态和胰岛素分泌有益。Wistar大鼠喂食标准或CAF饮食12周。随后，CAF大鼠随机接受迷走神经干切断术（CAF Vag）或假手术（CAF Sham）。CAF Sham大鼠是高吞噬、肥胖的，并且呈现代谢紊乱，包括高胰岛素血症、葡萄糖耐受不良、胰岛素抵抗、高血糖症和高胆固醇血症。迷走神经切断术后12周，CAF Vag大鼠体重和性腺周围脂肪储存减少。迷走神经切断术并不能改变葡萄糖耐量，但能使进食量、胰岛素血症和胰岛素敏感性正常化。从CAF假大鼠分离的胰岛分泌更多的胰岛素响应胆碱能剂，卡巴胆碱，当细胞内的环磷酸腺嘌呤（cAMP）被毛喉素或3-异丁基-1-甲基黄嘌呤增强。迷走神经切断术降低了葡萄糖诱导的胰岛素释放，这是由于对β细胞的胆碱能作用减少。这种作用也使响应cAMP的胰岛分泌正常化。因此，迷走神经切断术在大鼠喂养的CAF风格的饮食有效地减少肥胖和恢复胰岛素敏感性。这些影响主要与内分泌胰腺缺乏胆碱能作用有关，这会降低胰岛素血症，并可能逐渐减少脂肪储存和改善胰岛素敏感性。
Herein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on beta-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity.