Molecular mechanisms of insulin-and exercise-induced glucose uptake

胰岛素和运动诱导的葡萄糖摄取的分子机制

• 批准号: 14370334
• 负责人: ASANO Tomoichiro
• 金额: $ 9.6万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370334/
• 关键词: Insulin resistance; Diabetes; signal transduction; resistin; 糖代謝; インスリン; Akt; AMPK

It is well known that excessive salt intake induces elevation of blood pressure and that hypertension often coexists with insulin resistance. The contribution made by salt intake to the development of insulin resistance remains unclear, however. In this minireview, the insulin resistance seen in three salt-sensitive rat models (the high-salt-fed Sprague-Dawley rat, the Dahl salt sensitive rat and the chronically angiotensin II (AII)-infused rat) are presented. One notable observation common to all three models was that, despite their insulin-resistance, the early insulin signaling steps leading from activation of IR and IRSs to activation of PI 3-kinase Akt were apparently enhanced. This suggests that the molecular mechanism underlying the insulin resistance related to the salt-sensitive hypertension is unique. Other factors known to cause insulin resistance -e.g., obesity -actually suppress early insulin signaling, but for insulin resistance related to high salt intake, the impaired step must be further downstream in the insulin signaling pathway. What's more, increased oxidative stress appears to be crucially involved in both MI-and high-salt-induced insulin resistance.

众所周知，过多的盐摄入会导致血压升高，而高血压往往与胰岛素抵抗并存。然而，盐摄入对胰岛素抵抗发展的贡献仍不清楚。在这篇小综述中，介绍了三种盐敏感大鼠模型（高盐喂养的 Sprague-Dawley 大鼠、Dahl 盐敏感大鼠和长期注射血管紧张素 II (AII) 的大鼠）中观察到的胰岛素抵抗。所有三种模型共有的一个值得注意的观察结果是，尽管它们存在胰岛素抵抗，但从 IR 和 IRS 激活到 PI 3-激酶 Akt 激活的早期胰岛素信号转导步骤明显增强。这表明与盐敏感性高血压相关的胰岛素抵抗的分子机制是独特的。已知导致胰岛素抵抗的其他因素（例如肥胖）实际上会抑制早期胰岛素信号传导，但对于与高盐摄入相关的胰岛素抵抗，受损的步骤必须位于胰岛素信号传导途径的更下游。更重要的是，氧化应激的增加似乎与心肌梗死和高盐诱导的胰岛素抵抗密切相关。

项目成果

Ogihara, T., et al.: "Anguotension II-induced insulin resistance is associated with enhanced insulin signaling"Hypertension. 20. 872-879 (2002)

Ogihara, T. 等人：“Anguotension II 诱导的胰岛素抵抗与胰岛素信号传导增强有关”高血压。

Horike, N., et al.: "Salt-inducible kinase-2 : adipose-specific expression, phosphorylation of Ser-794 in insulin receptor substrate-I, and activation in diabetic animals"J.Biol.Chem.. 278(20). 18440-18447 (2003)

Horike, N. 等人：“盐诱导激酶 2：脂肪特异性表达、胰岛素受体底物 I 中 Ser-794 的磷酸化以及糖尿病动物中的激活”J.Biol.Chem.. 278(20

Fujishiro, M., et al.: "Three mitogen-activated protein kinases inhibit insulin signaling by different mechanisms in 3T3-L1 adipocytes"Mol. Endocrinol.. 17. 487-497 (2003)

Fujishiro, M. 等人：“三种丝裂原激活蛋白激酶在 3T3-L1 脂肪细胞中通过不同机制抑制胰岛素信号传导”Mol。

Yamamoto, A., et al.: "Suppression of arthritic bone destruction by adenovirus-mediated dominant negative ras gene transfer to synoviocytes and osteoclasts"Arthritis and Rheumatism.. 48(9). 2682-2692 (2003)

Yamamoto, A. 等人：“通过腺病毒介导的显性负性 ras 基因转移至滑膜细胞和破骨细胞来抑制关节炎骨质破坏”关节炎和风湿病.. 48(9)。

Ogihara, T., et al.: "Contribution of Salt Intake to Insulin Resistance Associated with Hypertension"Life Science. 73(5). 509 (2003)

Ogihara, T. 等人：“盐摄入量对与高血压相关的胰岛素抵抗的影响”生命科学。