Insulin Activates Erk1/2 Signaling in the Dorsal Vagal Complex to Inhibit Glucose Production
Insulin Activates Erk1/2 Signaling in the Dorsal Vagal Complex to Inhibit Glucose Production
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DOI：
10.1016/j.cmet.2012.09.005
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发表时间：
2012-10-01
期刊：
影响因子：
29
通讯作者：
Lam, Tony K. T.
中科院分区：
文献类型：
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作者：
Filippi, Beatrice M.;Yang, Clair S.;Lam, Tony K. T.
胰岛素激活PI 3-激酶（PI 3 K）/AKT以调节啮齿动物外周组织和下丘脑中基底膜（MBH）中的葡萄糖稳态。我们报告，胰岛素输注到MBH或背迷走神经复合体（DVC）激活胰岛素受体。激活MBH PI 3 K/AKT的胰岛素剂量对DVC无影响。DVC胰岛素反而激活了Erk 1/2，并降低了大鼠和小鼠的葡萄糖产量。DVC Erk 1/2的分子和化学抑制否定了DVC胰岛素的作用，而DVC Erk 1/2的激活概括了DVC胰岛素的作用。当正常啮齿类动物DVC Erk 1/2被抑制时，循环胰岛素不能抑制葡萄糖的产生，而在高脂喂养的啮齿类动物中DVC胰岛素作用被破坏。DVC ATP敏感性钾通道的激活是胰岛素-Erk 1/2所必需的，足以抑制正常和高脂喂养啮齿动物的葡萄糖产生。DVC是胰岛素作用的位点，其中胰岛素触发Erk 1/2信号传导以抑制葡萄糖产生和高脂肪喂养中的胰岛素抵抗。
Insulin activates PI3-kinase (PI3K)/AKT to regulate glucose homeostasis in the peripheral tissues and the mediobasal hypothalamus (MBH) of rodents. We report that insulin infusion into the MBH or dorsal vagal complex (DVC) activated insulin receptors. The same dose of insulin that activated MBH PI3K/AKT did not in the DVC. DVC insulin instead activated Erk1/2 and lowered glucose production in rats and mice. Molecular and chemical inhibition of DVC Erk1/2 negated, while activation of DVC Erk1/2 recapitulated, the effects of DVC insulin. Circulating insulin failed to inhibit glucose production when DVC Erk1/2 was inhibited in normal rodents, while DVC insulin action was disrupted in high-fat-fed rodents. Activation of DVC ATP-sensitive potassium channels was necessary for insulin-Erk1/2 and sufficient to inhibit glucose production in normal and high-fat-fed rodents. DVC is a site of insulin action where insulin triggers Erk1/2 signaling to inhibit glucose production and of insulin resistance in high-fat feeding.