Department of Internal Medicine II, University of Ulm, Germany.
Mol Cell Endocrinol. 2012 Apr 4;351(2):337-41. doi: 10.1016/j.mce.2012.01.011. Epub 2012 Jan 16.
Elevated levels of C-peptide have been found in patients with insulin resistance and early type 2 diabetes. These patients are at greater risk to develop micro- and macrovascular complications. Since diabetic nephropathy involves glomerular hyperproliferation, the present study evaluates the role of C-peptide on human renal mesangial cell proliferation.
C-peptide induces proliferation of human renal mesangial cells in a concentration-dependent manner with a maximal 2.6±0.4-fold induction at 10 nmol/L (P<0.05 compared with unstimulated cells; n=6), as revealed by [3H]-thymidine incorporation experiments. The proliferative effect of C-peptide is prevented by Src-kinase inhibitor-PP2, PI-3 kinase inhibitor-LY294002, and the ERK1/2 inhibitor-U126. Moreover, C-peptide induces phosphorylation of Src, as well as activation of PI-3 kinase and ERK1/2. Furthermore, C-peptide induces cyclin D1 expression as well as phosphorylation of retinoblastoma protein (Rb).
These results demonstrate an active role of C-peptide on the proliferation of human renal mesangial cells in vitro involving PI-3 kinase and MAP kinase signaling pathways, suggesting a possible role of C-peptide in glomerular hyperproliferation in patients with diabetic nephropathy.
在胰岛素抵抗和早期 2 型糖尿病患者中发现 C 肽水平升高。这些患者发生微血管和大血管并发症的风险更高。由于糖尿病肾病涉及肾小球过度增生，本研究评估 C 肽对人肾系膜细胞增殖的作用。
通过[3H]-胸苷掺入实验显示，C 肽以浓度依赖性方式诱导人肾系膜细胞增殖，在 10 nmol/L 时最大诱导 2.6±0.4 倍（与未刺激细胞相比，P<0.05；n=6）。C 肽的增殖作用可被Src 激酶抑制剂-PP2、PI-3 激酶抑制剂-LY294002 和 ERK1/2 抑制剂-U126 阻断。此外，C 肽诱导 Src 的磷酸化，以及 PI-3 激酶和 ERK1/2 的激活。此外，C 肽诱导细胞周期蛋白 D1 的表达以及视网膜母细胞瘤蛋白（Rb）的磷酸化。
这些结果表明 C 肽在体外对人肾系膜细胞的增殖具有积极作用，涉及 PI-3 激酶和 MAP 激酶信号通路，提示 C 肽在糖尿病肾病患者肾小球过度增生中可能发挥作用。
