CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay F-91405, France.
Mol Cell Endocrinol. 2012 Mar 5;350(1):136-44. doi: 10.1016/j.mce.2011.12.007. Epub 2011 Dec 19.
Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a diabetic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin-serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.
血清素和胰岛素是下丘脑体内平衡机制的关键调节因子。然而，在 2 型糖尿病中，下丘脑对血清素的反应性尚不清楚。我们使用糖尿病模型——Goto Kakizaki（GK）大鼠，通过 Akt 磷酸化来探讨下丘脑和肝脏中胰岛素受体表达、胰岛素和血清素效率。胰岛素或右芬氟拉明（血清素刺激剂）处理可诱导 Wistar 大鼠的 Akt 磷酸化，但不能诱导表现出下调胰岛素受体的 GK 大鼠的 Akt 磷酸化。神经母细胞瘤细胞系的研究表明，血清素诱导的 Akt 磷酸化依赖于 PI3-激酶。最后，在进食反应中，GK 大鼠下丘脑的血清素释放减少，表明这种神经递质的反应性受损。总之，糖尿病 GK 大鼠的下丘脑血清素和胰岛素效率受损。在糖尿病发生过程中，观察到的这种胰岛素-血清素相互作用和损伤可能是大脑中的一个潜在关键改变。
