Nordquist Lina, Wahren John
Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, 75123 Uppsala, Sweden.
Rev Diabet Stud. 2009 Fall;6(3):203-10. doi: 10.1900/RDS.2009.6.203. Epub 2009 Nov 10.
Proinsulin C-peptide has been found to exert beneficial effects in many tissues affected by diabetic microvascular complications, including the kidneys. Glomerular hyperfiltration and microalbuminuria are early markers of diabetic nephropathy. C-peptide at physiological concentrations effectively reduces diabetes-induced glomerular hyperfiltration via constriction of the afferent arteriole, dilation of the efferent arteriole, and inhibition of tubular reabsorption in experimental models of type 1 diabetes. The glomerular hypertrophy and mesangial matrix expansion seen in early diabetes can be reduced or prevented by C-peptide administration, possibly via interference with TGF-beta1 and TNFalpha signaling. Several of C-peptide's reno-protective effects have been confirmed in human studies; reduced glomerular hyperfiltration and diminished urinary albumin excretion have been documented in type 1 diabetes patients receiving replacement doses of C-peptide for periods of up to 3 months. In this review, we critically summarize the current state of knowledge regarding C-peptide's renal effects, and discuss possible mechanisms of its beneficial effects in diabetic nephropathy.
胰岛素原C肽已被发现在许多受糖尿病微血管并发症影响的组织中发挥有益作用，包括肾脏。肾小球高滤过和微量白蛋白尿是糖尿病肾病的早期标志物。在1型糖尿病实验模型中，生理浓度的C肽可通过入球小动脉收缩、出球小动脉扩张以及抑制肾小管重吸收，有效降低糖尿病诱导的肾小球高滤过。早期糖尿病中出现的肾小球肥大和系膜基质扩张可通过给予C肽来减轻或预防，这可能是通过干扰转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α（TNFα）信号通路实现的。C肽的几种肾脏保护作用已在人体研究中得到证实；在接受长达3个月替代剂量C肽的1型糖尿病患者中，已记录到肾小球高滤过降低和尿白蛋白排泄减少。在本综述中，我们批判性地总结了关于C肽肾脏作用的当前知识状态，并讨论了其在糖尿病肾病中发挥有益作用的可能机制。
