Apelin targets gut contraction to control glucose metabolism via the brain
Apelin targets gut contraction to control glucose metabolism via the brain
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DOI：
10.1136/gutjnl-2015-310230
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发表时间：
2017-02-01
期刊：
影响因子：
24.5
通讯作者：
Knauf, Claude
中科院分区：
文献类型：
--
作者：
Fournel, Audren;Drougard, Anne;Knauf, Claude
目的肠脑轴被认为是控制葡萄糖稳态的主要调控检查点。十二指肠中营养物质和/或激素的检测使下丘脑了解宿主的营养状况。这一过程可能通过下丘脑神经元调节一氧化氮（NO）的中枢释放而发生，一氧化氮反过来控制葡萄糖进入组织。肠神经系统（ENS）在各种刺激下调节肠道收缩，但这种相互作用在通过大脑控制葡萄糖稳态中的重要性尚不清楚。我们研究了存在于肠道中的生物活性肽apelin是否调节ens诱发的收缩，从而确定了通过下丘脑控制葡萄糖利用的新生理伙伴。我们通过遥测探针和等渗传感器测量了正常和肥胖/糖尿病小鼠中apelin对十二指肠电和机械反应的影响。下丘脑一氧化氮释放的变化，响应十二指肠收缩由胰尖蛋白调节，以特定的电流探针实时评估。通过口服放射性标记的葡萄糖来测量组织中的葡萄糖利用率。结果在正常小鼠和肥胖/糖尿病小鼠中，响应于apelin的ENS/收缩活动减少，从而增加下丘脑NO释放，葡萄糖利用得到改善。因此，葡萄糖在肌肉中的进入量显著增加。在这里，我们确定了肠道和下丘脑之间控制葡萄糖利用的一种新的通信模式。此外，我们的数据表明口服apelin是治疗代谢紊乱的一个新的潜在靶点。
Objective The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus.Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose.Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle.Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders.