Cross-talk between the insulin and leptin signaling systems in rat hypothalamus
Cross-talk between the insulin and leptin signaling systems in rat hypothalamus
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DOI：
10.1038/oby.2005.7
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Saad, MJA
中科院分区：
文献类型：
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作者：
Carvalheira, JBC;Torsoni, MA;Saad, MJA
目的：调查是否胰岛素和瘦素共享共同的细胞内信号转导通路，并确定这些激素信号系统是否调节对方的行动在大鼠hypothalamus.Research Methods和Procedures：雄性Wistar大鼠进行了研究后，慢性植入的脑室内导管到第三脑室。采用免疫沉淀和免疫印迹法检测大鼠下丘脑中胰岛素和瘦素信号分子的活化。单独的胰岛素能够产生胰岛素受体底物（IRS）/磷脂酰肌醇3-激酶的分子活化（PI 3-激酶）/Akt和丝裂原活化蛋白（MAP）激酶信号通路，而单独的瘦素激活MAP激酶和IRS/PI 3-激酶信号而不影响Akt。瘦素和胰岛素的联合输注会产生双重作用。没有任何单一激素对胰岛素信号传导途径、IRS/PI 3-激酶/Akt和MAP激酶的作用的定量增强。相反，瘦素加胰岛素导致定量增强的分子信号传导通过Janus激酶/信号转导和转录pathway.Discussion的激活：我们提供的证据瘦素和胰岛素信号的收敛在IRS-PI 3-激酶的水平和Akt的水平分歧。此外，我们的研究结果表明，在Janus激酶2和信号转导和转录激活因子3酪氨酸磷酸化水平上，胰岛素和瘦素之间存在直接和积极的串扰。这种机制可能有助于增强胰岛素和瘦素途径的活性，并增加生理过程中的刺激，例如控制食物摄入和体重，这些过程受胰岛素和瘦素的联合控制。
Objective: To investigate whether insulin and leptin share common intracellular signal transduction pathways and to determine whether these hormonal signaling systems modulate each other's action in rat hypothalamus.Research Methods and Procedures: Male Wistar rats were studied after chronic implantation of an intracerebroventricular catheter into the third ventricle. Immunoprecipitation and immunoblotting were used to examine the activation of insulin and leptin signaling molecules in the rat hypothalamus.Results: Insulin alone is able to produce molecular activation of insulin receptor substrates (IRS s)/phosphatidylinositol 3-kinase (PI 3-kinase)/Akt and mitogen-activated protein (MAP) kinase signaling pathways in hypothalamus, whereas leptin alone activates MAP kinase and IRSs/PI 3-kinase signaling with no effect on Akt. Combined infusion of leptin and insulin provokes a dual action. There was no quantitative potentialization of any single hormone's action on the elements of the insulin signaling pathway, IRSs/PI 3-kinase/Akt, and MAP kinase. Conversely, leptin plus insulin leads to quantitative potentialization of molecular signaling through the Janus kinase/signal transducer and activator of transcription pathway.Discussion: We provide evidence for a convergence of leptin and insulin signaling at the level of IRSs-PI 3-kinase and a divergence at the level of Akt. Moreover, our results indicate a direct and positive cross-talk between insulin and leptin at the level of Janus.kinase 2 and signal transducer and activator of transcription 3 tyrosine phosphorylation. This mechanism may serve to potentiate the activity of both insulin and leptin pathways and to increase stimulation in physiological processes such as the control of food intake and body weight, which are under the combined control of insulin and leptin.