Central Apelin Controls Glucose Homeostasis via a Nitric Oxide-Dependent Pathway in Mice
Central Apelin Controls Glucose Homeostasis via a Nitric Oxide-Dependent Pathway in Mice
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DOI：
10.1089/ars.2010.3454
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发表时间：
2011-09-01
影响因子：
6.6
通讯作者：
Knauf, Claude
中科院分区：
文献类型：
--
作者：
Duparc, Thibaut;Colom, Andre;Knauf, Claude
目的：Apelin及其受体已成为治疗胰岛素抵抗的有希望的靶点。事实上，爱帕琳的外周施用通过一氧化氮（NO）途径刺激葡萄糖利用和胰岛素敏感性。除了在外周代谢活性脂肪组织上表达外，爱帕琳还在脑中发现。然而，没有关于爱帕琳对代谢控制的中枢作用的数据。我们研究了急性和慢性脑室内（i. c. v.）在正常和肥胖/糖尿病小鼠中进行apelin注射。结果：我们证明，i. c. v.注射爱帕琳到喂养的小鼠通过NO依赖性机制改善葡萄糖控制。这些结果已通过转基因（eNOS-KO小鼠）、药理学（L-NMMA i. c. v.处理的小鼠）和使用安培探针检测的NO释放的实时测量得到加强。高脂饮食喂养的小鼠显示出对i. c. v.爱帕琳肽的反应严重迟钝，与下丘脑缺乏NO反应相关。此外，在禁食的正常小鼠中集中施用高剂量爱帕琳引起高胰岛素血症、高血糖症、葡萄糖耐受不良和胰岛素抗性。结论：这些数据提供了令人信服的证据表明，中央爱帕琳参与葡萄糖稳态的调节，并提出了一种新的病理生理机制，参与从正常到糖尿病状态的转变。抗氧化剂。氧化还原信号。15，1477-1496.
Aims: Apelin and its receptor have emerged as promising targets for the treatment of insulin resistance. Indeed, peripheral administration of apelin stimulates glucose utilization and insulin sensitivity via a nitric oxide (NO) pathway. In addition to being expressed on peripheral metabolically active adipose tissues, apelin is also found in the brain. However, no data are available on the role of central effects of apelin on metabolic control. We studied glucose metabolism in response to acute and chronic intracerebroventricular (i.c.v.) injection of apelin performed in normal and obese/diabetic mice. Results: We demonstrate that i.c.v. injection of apelin into fed mice improves glucose control via NO-dependent mechanisms. These results have been strengthened by transgenic (eNOS-KO mice), pharmacological (L-NMMA i.c.v. treated mice), and real-time measurement of NO release with amperometric probes detection. High-fat diet-fed mice displayed a severely blunted response to i.c.v. apelin associated with a lack of NO response by the hypothalamus. Moreover, central administration of high dose apelin in fasted normal mice provoked hyperinsulinemia, hyperglycemia, glucose intolerance, and insulin resistance. Conclusion: These data provide compelling evidence that central apelin participates in the regulation of glucose homeostasis and suggest a novel pathophysiological mechanism involved in the transition from normal to diabetic state. Antioxid. Redox Signal. 15, 1477-1496.