The involvement of aldosterone on vascular insulin resistance: implications in obesity and type 2 diabetes.
The involvement of aldosterone on vascular insulin resistance: implications in obesity and type 2 diabetes.
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DOI：
10.1186/1758-5996-6-90
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发表时间：
2014
影响因子：
4.8
通讯作者：
Tostes RC
中科院分区：
文献类型：
--
作者：
Bruder-Nascimento T;da Silva MA;Tostes RC
醛固酮是一种在肾上腺产生的矿物质皮质激素，它控制着体液电解质的平衡，因此在血压调节中起着关键作用。醛固酮还直接作用于许多器官，包括血管系统，导致许多细胞事件，影响增殖、迁移、炎症、氧化还原平衡和细胞凋亡。醛固酮的作用依赖于它与盐皮质激素受体(MR)的结合。醛固酮与MR结合可触发两条途径，即基因组途径和非基因组途径。例如，在血管系统中，醛固酮激活非基因组途径会引起迅速的效应，包括激活激酶、磷酸酶、转录因子和NAD(P)H氧化酶。醛固酮在全身和血管胰岛素抵抗中也起着关键作用，即组织无法对胰岛素做出反应。胰岛素对细胞功能有重要作用，血管胰岛素抵抗被认为是血管损伤的早期因素。相应地，醛固酮通过改变磷脂酰肌醇3-激酶(PI3K)/一氧化氮(NO)途径，诱导氧化应激和胰岛素样生长因子-1受体(IGF-1R)之间的串扰，从而损害胰岛素受体(IR)信号转导。本文就醛固酮与血管胰岛素抵抗的关系作一综述。还讨论了MR拮抗剂作为治疗工具减少肥胖和2型糖尿病相关血管损伤的证据。
Aldosterone, a mineralocorticoid hormone produced at the adrenal glands, controls corporal hydroelectrolytic balance and, consequently, has a key role in blood pressure adjustments. Aldosterone also has direct effects in many organs, including the vasculature, leading to many cellular events that influence proliferation, migration, inflammation, redox balance and apoptosis. Aldosterone effects depend on its binding to mineralocorticoid receptors (MR). Aldosterone binding to MR triggers two pathways, the genomic pathway and the non-genomic pathway. In the vasculature e.g., activation of the non-genomic pathway by aldosterone induces rapid effects that involve activation of kinases, phosphatases, transcriptional factors and NAD(P)H oxidases. Aldosterone also plays a crucial role on systemic and vascular insulin resistance, i.e. the inability of a tissue to respond to insulin. Insulin has a critical role on cell function and vascular insulin resistance is considered an early contributor to vascular damage. Accordingly, aldosterone impairs insulin receptor (IR) signaling by altering the phosphatidylinositol 3-kinase (PI3K)/nitric oxide (NO) pathway and by inducing oxidative stress and crosstalk between the IR and the insulin-like growth factor-1 receptor (IGF-1R). This mini-review focuses on the relationship between aldosterone and vascular insulin resistance. Evidence indicating MR antagonists as therapeutic tools to minimize vascular injury associated with obesity and diabetes type 2 is also discussed.
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