Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.
Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.
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在喂食高钠饮食的情况下，γ-黑素细胞刺激激素信号基因中断的高血压小鼠的葡萄糖代谢异常。
DOI：
10.1038/ajh.2008.290
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发表时间：
2008
影响因子：
3.2
通讯作者：
Humphreys,MichaelH
中科院分区：
文献类型：
--
作者：
Ni,X-P;Humphreys,MichaelH
背景缺乏或抵抗阿片黑皮质素原衍生肽γ-黑素细胞刺激激素（γ-MSH）的啮齿类动物会出现明显的盐敏感性高血压。我们询问这种高血压是否伴有异常的葡萄糖代谢。方法对γ-MSH缺陷型Pc2−/−小鼠和耐药Mc3r−/−小鼠进行了严格研究，以测量高钠饮食（HSD；8% NaCl）与正常钠饮食（NSD；0.4% NaCl）≥1周后的血压、葡萄糖和胰岛素浓度。 Mc3r−/−还进行了葡萄糖耐量试验（GTT）和胰岛素耐量试验。结果两种基因敲除菌株均患有高血压，并且在HSD上也表现出空腹高血糖和高胰岛素血症。与HSD或NSD的野生型小鼠或NSD的Mc3r−/−小鼠相比，HSD的Mc3r−/−小鼠的葡萄糖耐量和胰岛素介导的葡萄糖处理受损。 结论这些结果表明，γ-MSH信号传导中断与HSD相互作用，一方面导致高血压，另一方面导致葡萄糖代谢异常，具有胰岛素抵抗的特征。对这种相互作用本质的进一步研究应该为盐敏感性高血压和胰岛素抵抗之间的联系机制提供新的见解。
BackgroundRodents with deficiency of or resistance to the proopiomelanocortin-derived peptide γ-melanocyte stimulating hormone (γ-MSH) develop marked salt-sensitive hypertension. We asked whether this hypertension was accompanied by abnormal glucose metabolism.Methodsγ-MSH-deficient Pc2−/−mice, and resistant Mc3r−/−mice were studied acutely for measurement of blood pressure and glucose and insulin concentrations after ≥1 week of a high-sodium diet (HSD; 8% NaCl) compared to a normal-sodium diet (NSD; 0.4% NaCl). Mc3r−/−also underwent glucose tolerance test (GTT) and insulin tolerance test.ResultsBoth knockout strains were hypertensive and also exhibited fasting hyperglycemia and hyperinsulinemia on the HSD. Mc3r−/−mice on the HSD had impaired glucose tolerance and insulin-mediated glucose disposal compared to wild-type mice on either the HSD or the NSD, or to Mc3r−/−mice on the NSD.ConclusionsThese results indicate an interaction of interrupted γ-MSH signaling with the HSD to cause hypertension on the one hand and abnormal glucose metabolism, with the characteristics of insulin resistance, on the other. Further study of the nature of this interaction should provide new insight into the mechanisms by which salt-sensitive hypertension and insulin resistance are linked.