Ni X-P, Humphreys Michael H
Division of Nephrology, San Francisco General Hospital, San Francisco, CA, USA.
Am J Hypertens. 2008 Dec;21(12):1284-7. doi: 10.1038/ajh.2008.290. Epub 2008 Sep 18.
Rodents with deficiency of or resistance to the proopiomelanocortin-derived peptide gamma-melanocyte stimulating hormone (gamma-MSH) develop marked salt-sensitive hypertension. We asked whether this hypertension was accompanied by abnormal glucose metabolism.
gamma-MSH-deficient Pc2(-/-) mice, and resistant Mc3r(-/-) mice were studied acutely for measurement of blood pressure and glucose and insulin concentrations after > or =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.
Both 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.
These results indicate an interaction of interrupted gamma-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.
缺乏促阿片-黑素细胞皮质素衍生肽γ-黑素细胞刺激素（γ-MSH）或对其有抵抗性的啮齿动物会出现明显的盐敏感性高血压。我们探究了这种高血压是否伴有糖代谢异常。
对γ-MSH缺陷型Pc2(-/-)小鼠和抵抗型Mc3r(-/-)小鼠进行急性研究，在高钠饮食（HSD；8%氯化钠）≥1周后，与正常钠饮食（NSD；0.4%氯化钠）相比，测量其血压、血糖和胰岛素浓度。Mc3r(-/-)小鼠还进行了葡萄糖耐量试验（GTT）和胰岛素耐量试验。
两种基因敲除品系均出现高血压，且在高钠饮食时还表现出空腹高血糖和高胰岛素血症。与高钠饮食或正常钠饮食的野生型小鼠相比，或与正常钠饮食的Mc3r(-/-)小鼠相比，高钠饮食的Mc3r(-/-)小鼠葡萄糖耐量受损，胰岛素介导的葡萄糖处置能力下降。
这些结果表明，γ-MSH信号中断与高钠饮食相互作用，一方面导致高血压，另一方面导致具有胰岛素抵抗特征的糖代谢异常。对这种相互作用本质的进一步研究应能为盐敏感性高血压与胰岛素抵抗之间的联系机制提供新的见解。
