Effects of C-peptide on microvascular blood flow and blood hemorheology.
Effects of C-peptide on microvascular blood flow and blood hemorheology.
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C肽对微血管血流和血液流行病学的影响。
DOI：
10.1080/15438600490424532
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发表时间：
2004-01
期刊：
影响因子：
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通讯作者：
Kunt, T
中科院分区：
文献类型：
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作者：
Forst, T;Kunt, T
除了血管生物学的功能和结构改变外，血细胞流变学特性的改变主要决定了糖尿病患者微血管血流受损。最近的研究提供了越来越多的证据表明，1型糖尿病患者c肽分泌受损可能导致微血管并发症的发生。c肽已被证明通过激活Ca2+钙调磷酸酶eNOS来刺激内皮细胞NO分泌。NO本身具有提高平滑肌细胞cGMP水平和激活Na+ K+ atp酶活性的能力，因此在微血管调节中发挥了许多作用。在1型糖尿病患者中，补充c肽被证明可以改善不同血管室中一氧化氮依赖途径的内皮依赖性血管舒张。此外，研究表明，在1型糖尿病患者中使用c肽，通过增加营养毛细血管血流量而有利于乳头下血流量，导致皮肤血流量的重新分配。Na+ K+ atp酶受损是糖尿病的另一个特征，被认为是多种细胞功能的关键调节因子。在体外和体内研究中，c肽补充已被证明可以恢复不同细胞类型的Na+ K+ atp酶活性。在1型糖尿病患者中，补充c肽可使红细胞Na+ K+ atp酶活性提高约100%。血浆c肽水平与红细胞Na+ K+ atp酶活性呈线性关系。在小毛细血管中，微血管血流越来越多地由红细胞的流变学特性决定。应用激光衍射观察，1型糖尿病患者给予c肽后红细胞变形能力明显改善。Obain对Na+ K+ atp酶的抑制完全消除了c肽对红细胞变形能力的影响。综上所述，c肽通过干扰微血管血流的血管和流变学成分改善1型糖尿病患者的微血管功能和血流。
Beside functional and structural changes in vascular biology, alterations in the rheologic properties of blood cells mainly determines to an impaired microvascular blood flow in patients suffering from diabetes mellitus. Recent investigations provide increasing evidence that impaired C-peptide secretion in type 1 diabetic patients might contribute to the development of microvascular complications. C-peptide has been shown to stimulate endothelial NO secretion by activation of the Ca2+ calmodolin regulated enzyme eNOS. NO himself has the potency to increase cGMP levels in smooth muscle cells and to activate Na+ K+ ATPase activity and therefore evolves numerous effects in microvascular regulation. In type 1 diabetic patients, supplementation of C-peptide was shown to improve endothelium dependent vasodilatation in an NO-dependent pathway in different vascular compartments. In addition, it could be shown that C-peptide administration in type 1 diabetic patients, results in a redistribution of skin blood flow by increasing nutritive capillary blood flow in favour to subpapillary blood flow. Impaired Na+ K+ ATPase in another feature of diabetes mellitus in many cell types and is believed to be a pivotal regulator of various cell functions. C-peptide supplementation has been shown to restore Na+ K+ATPase activity in different cell types during in vitro and in vivo investigations. In type 1 diabetic patients, C-peptide supplementation was shown to increase erythrocyte Na+ K+ATPase activity by about 100%. There was found a linear relationship between plasma C-peptide levels and erythrocyte Na+ K+ATPase activity. In small capillaries, microvascular blood flow is increasingly determined by the rheologic properties of erythrocytes. Using laser-diffractoscopie a huge improvement in erythrocyte deformability could be observed after C-peptide administration in erythrocytes of type 1 diabetic patients. Inhibition of the Na+ K+ATPase by Obain completely abolished the effect of C-peptide on erythrocyte deformability. In conclusion, C-peptide improves microvascular function and blood flow in type 1 diabetic patients by interfering with vascular and rheological components of microvascular blood flow.