Caillaud K, Boisseau N, Ennequin G, Chavanelle V, Etienne M, Li X, Denis P, Dardevet D, Lacampagne A, Sirvent P
Université Clermont-Auvergne, université Blaise-Pascal, EA 3533, laboratoire des adaptations métaboliques à l'exercice en conditions physiologiques et pathologiques (AME2P), BP 80026, 63171 Aubière cedex, France; CRNH-Auvergne, 63001 Clermont-Ferrand, France.
Zensun Sci & Tech Ltd., Shanghai, China.
Diabetes Metab. 2016 Apr;42(2):96-104. doi: 10.1016/j.diabet.2015.08.003. Epub 2015 Sep 26.
Studies both in vitro and ex vivo of rodent skeletal muscle have highlighted the potential involvement of neuregulin 1 (NRG1) in glucose metabolism regulation, yet nothing is known of the role of NRG1 in systemic glucose homoeostasis. For this reason, it was hypothesized that systemic delivery of NRG1 might improve glucose tolerance and that the effect might be age-dependent.
Glucose tolerance tests were performed in 6-month-old (adult) and 22-month-old (old) male Wistar rats 15min after a single injection of either NRG1 (50μg/kg) or saline (controls). Skeletal muscle and liver samples were also collected 30min after the acute NRG1 or saline treatment, while the phosphorylation status of ErbB receptors and AKT was assessed by Western blotting.
Acute NRG1 treatment decreased the glycaemic response to an oral glucose load in both adult and old rats. NRG1 injection did not activate ErbB receptors in skeletal muscle, whereas phosphorylation of ErbB3 and AKT was markedly increased in the liver of NRG1-treated adult and old rats compared with controls.
This study shows that NRG1 has a possible glucose-lowering effect in the liver and via an ErbB3/AKT signaling pathway. This NRG1 effect is also maintained in old rats, suggesting that the NRG1/ErbB signaling pathway might represent a promising therapeutic target in insulin resistance states.
啮齿动物骨骼肌的体外和离体研究均突出了神经调节蛋白1（NRG1）在葡萄糖代谢调节中的潜在作用，但对于NRG1在全身葡萄糖稳态中的作用尚不清楚。因此，有人提出假设，全身性给予NRG1可能会改善葡萄糖耐量，且这种作用可能具有年龄依赖性。
对6月龄（成年）和22月龄（老年）雄性Wistar大鼠单次注射NRG1（50μg/kg）或生理盐水（对照组）15分钟后进行葡萄糖耐量试验。在急性给予NRG1或生理盐水治疗30分钟后，还收集骨骼肌和肝脏样本，同时通过蛋白质免疫印迹法评估ErbB受体和AKT的磷酸化状态。
急性NRG1治疗降低了成年和老年大鼠对口服葡萄糖负荷的血糖反应。NRG1注射未激活骨骼肌中的ErbB受体，而与对照组相比，NRG1治疗的成年和老年大鼠肝脏中ErbB3和AKT的磷酸化明显增加。
本研究表明，NRG1在肝脏中可能具有降血糖作用，并通过ErbB3/AKT信号通路发挥作用。老年大鼠中也维持了这种NRG1效应，这表明NRG1/ErbB信号通路可能是胰岛素抵抗状态下一个有前景的治疗靶点。
