Haneda M, Kikkawa R, Koya D, Uzu T, Maeda S, Togawa M, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kidney Int. 1993 Sep;44(3):518-26. doi: 10.1038/ki.1993.276.
To test the hypothesis that the function of glomerular mesangial cells is impaired in diabetes, we examined the responsiveness of mesangial cells cultured under high concentrations of glucose to atrial natriuretic peptide (ANP1) and angiotensin II (Ang II). The ANP-induced accumulation of cGMP was enhanced in mesangial cells cultured under high glucose conditions, possibly due to the activation of particulate guanylate cyclase. Ang II action in mesangial cells was evaluated by measuring the ability of Ang II to inhibit ANP-induced cGMP accumulation through both activating phosphodiesterase (initial phase) and inhibiting guanylate cyclase (maintenance phase). The inhibition of both ANP-induced cellular cGMP accumulation and particulate guanylate cyclase activity by Ang II was significantly reduced in mesangial cells cultured under high concentrations of glucose. Moreover, in the cells exposed to high concentrations of glucose, both basal and Ang II-stimulated levels of inositol 1,4,5-trisphosphate (IP3) were significantly reduced. These results indicate that, in high glucose conditions, the actions of ANP and Ang II are modulated differently, resulting in the impairment of contractile responsiveness of mesangial cells.
为了验证糖尿病患者肾小球系膜细胞功能受损这一假说，我们检测了在高浓度葡萄糖条件下培养的系膜细胞对心钠素（ANP1）和血管紧张素II（Ang II）的反应性。在高糖条件下培养的系膜细胞中，ANP诱导的cGMP积累增加，这可能是由于颗粒型鸟苷酸环化酶的激活所致。通过测量Ang II通过激活磷酸二酯酶（初始阶段）和抑制鸟苷酸环化酶（维持阶段）来抑制ANP诱导的cGMP积累的能力，评估了Ang II在系膜细胞中的作用。在高浓度葡萄糖条件下培养的系膜细胞中，Ang II对ANP诱导的细胞cGMP积累和颗粒型鸟苷酸环化酶活性的抑制作用均显著降低。此外，在暴露于高浓度葡萄糖的细胞中，基础和Ang II刺激的肌醇1,4,5-三磷酸（IP3）水平均显著降低。这些结果表明，在高糖条件下，ANP和Ang II的作用受到不同调节，导致系膜细胞收缩反应性受损。
