The role of α1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation.
The role of α1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation.
复制标题
α1-肾上腺素能受体在调节代谢中的作用：增加葡萄糖耐量、瘦素分泌和脂质氧化。
DOI：
10.1080/10799893.2016.1193522
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Perez,DianneM
中科院分区：
文献类型：
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作者：
Shi,Ting;Papay,RobertS;Perez,DianneM
α1-肾上腺素能受体（α1-AR）及其亚型在代谢中的作用尚不清楚。大多数先前的研究是在转基因小鼠模型出现之前进行的，并利用转化的细胞系和选择性差的拮抗剂。我们现在研究了α1A-和α1B-AR亚型在存活敲除（KO）和表达组成型活性突变体（CAM）受体的转基因小鼠中的代谢调节，评估了亚型选择性功能。CAM小鼠增加葡萄糖耐量，而KO小鼠显示葡萄糖耐量受损。CAM小鼠增加了白色脂肪组织和骨骼肌的葡萄糖摄取，而KO降低了葡萄糖摄取，CAM α1A-AR显示出选择性葡萄糖摄取进入心脏。使用间接量热法，两种CAM小鼠表现出全身脂肪酸氧化增加，而KO小鼠优先氧化碳水化合物。CAM α1A-AR小鼠的空腹血浆甘油三酯和葡萄糖水平显著降低，而α1A-AR KO小鼠的甘油三酯和葡萄糖水平升高。两种CAM小鼠均表现出血浆瘦素水平升高，而KO小鼠瘦素水平降低。α1A-AR亚型的大多数代谢效应更有效。我们的研究结果表明，刺激α1-AR导致葡萄糖耐量增加，心脏葡萄糖摄取，瘦素分泌和全身脂质代谢增加的有利代谢特征，这可能有助于其先前公认的心脏保护和神经保护益处。
The role of α1-adrenergic receptors (α1-ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the α1A- and α1B-AR subtypesin vivousing knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance. CAM mice increased while KO decreased glucose uptake into white fat tissue and skeletal muscle with the CAM α1A-AR showing selective glucose uptake into the heart. Using indirect calorimetry, both CAM mice demonstrated increased whole body fatty acid oxidation, while KO mice preferentially oxidized carbohydrate. CAM α1A-AR mice displayed significantly decreased fasting plasma triglycerides and glucose levels while α1A-AR KO displayed increased levels of triglycerides and glucose. Both CAM mice displayed increased plasma levels of leptin while KO mice decreased leptin levels. Most metabolic effects were more efficacious with the α1A-AR subtype. Our results suggest that stimulation of α1-ARs results in a favorable metabolic profile of increased glucose tolerance, cardiac glucose uptake, leptin secretion and increased whole body lipid metabolism that may contribute to its previously recognized cardioprotective and neuroprotective benefits.