Effects of aldosterone on insulin sensitivity and secretion.
Effects of aldosterone on insulin sensitivity and secretion.
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DOI：
10.1016/j.steroids.2014.08.016
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发表时间：
2014-12
期刊：
影响因子：
2.7
通讯作者：
Luther JM
中科院分区：
文献类型：
--
作者：
Luther JM
康恩博士最初在20世纪50年代报道了醛固酮增多症患者患糖尿病的风险增加，尽管其机制尚不清楚。醛固酮诱导的低钾血症最初被描述为通过损害胰岛素分泌而损害葡萄糖耐量。然而，通过补钾纠正低钾血症只能部分恢复胰岛素分泌和葡萄糖耐量。醛固酮还通过活性氧以盐皮质激素受体非依赖性方式损害葡萄糖刺激的胰岛分泌。醛固酮诱导的盐皮质激素受体活化也损害脂肪细胞和骨骼肌的胰岛素敏感性。醛固酮可能通过改变钾、增加炎性细胞因子和减少有益的脂肪因子如脂联素而产生继发性胰岛素抵抗。在临床试验中，肾素-血管紧张素系统拮抗剂可降低循环中的醛固酮浓度以及2型糖尿病的风险。这些数据表明，原发性和继发性醛固酮增多症可能通过损害人体胰岛素敏感性或胰岛素分泌而导致葡萄糖耐量恶化。未来的研究应确定MR拮抗剂和醛固酮对人体胰岛素分泌和敏感性的影响。
Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950’s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentrations and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans.
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