Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism
Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism
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DOI：
10.1152/ajpregu.00811.2007
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发表时间：
2008-03-01
期刊：
影响因子：
--
通讯作者：
Persson, A. Erik G.
中科院分区：
文献类型：
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作者：
Nordquist, Lina;Lai, En Yin;Persson, A. Erik G.
目的：肾小球滤过率（GFR）升高被认为是糖尿病肾病进展的一个潜在机制。研究表明，c肽对糖尿病有保护肾的作用。该肽可降低1型糖尿病患者以及糖尿病动物模型中的超滤过。在这项研究中，我们研究了c肽是否引起小动脉直径的变化。研究设计与方法：实验前2周单次静脉注射四氧嘧啶使C57-B1小鼠发生糖尿病。年龄匹配的正常血糖小鼠作为对照。与肾小球完整的传入小动脉被切开并微灌注。研究了c肽在腔内应用的效果，并与炒c肽或载体进行了比较。研究了rho激酶抑制剂Y-27632的作用。结果：与对照组相比，c肽使糖尿病小鼠传入小动脉收缩-27%。给予c肽的正常血糖小动脉表现出延迟和分钟反应（-4%）。无论是给高血糖小鼠还是正常血糖小鼠，打乱c肽或给药均未引起任何影响。Y-27632的加入消除了c肽的作用。结论：c肽诱导糖尿病小鼠传入小动脉收缩。这可以降低GFR的升高，可能是c肽在糖尿病中保护肾脏的机制之一。
Objective: an increased glomerular filtration rate (GFR) has been postulated as a potential mechanism involved in the progression of diabetic nephropathy. Studies suggest that C-peptide exerts a renoprotective effect on diabetes. The peptide decreases hyperfiltration in patients with type 1 diabetes, as well as in diabetic animal models. In this study, we investigated whether C-peptide causes a change in arteriolar diameter.Research Design and Methods: C57-B1 mice were made diabetic by means of a single intravenous injection of alloxan 2 wk prior to the experiment. Age-matched normoglycemic mice served as controls. Afferent arterioles, intact with the glomeruli, were dissected and microperfused. The effect of luminal application of C-peptide, compared with scrambled C-peptide or vehicle, was investigated. The effect of the Rho-kinase inhibitor Y-27632 was also investigated.Results: C-peptide constricted afferent arterioles in diabetic mice by -27% compared with the control value. Normoglycemic arterioles administered C-peptide displayed a delayed and minute response (-4%). Scrambled C-peptide or vehicle administration, whether administered to hyperglycemic or normoglycemic mice, did not induce any effect. Addition of Y-27632 abolished the effect of C-peptide.Conclusion: C-peptide induces constriction of afferent arterioles in diabetic mice. This can reduce enhanced GFR and may be one of the mechanisms in the renoprotective action of C-peptide in diabetes.