Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with type 2 diabetes mellitus: association with progress of diabetic nephropathy

Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with type 2 diabetes mellitus: association with progress of diabetic nephropathy
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DOI:
10.1016/j.peptides.2004.06.024
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发表时间:
2004-10-01
期刊:
影响因子:
3
通讯作者:
Imai, Y
Imai, Y
中科院分区:
医学3区
文献类型:
--
作者:
Totsune, K;Takahashi, K;Imai, Y

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尾加压素II(UII)是迄今发现的最有效的血管收缩多肽。为了阐明尿路感染在糖尿病中的病理生理作用,我们检测了10例正常对照组和48例2型糖尿病患者的血浆免疫反应性尿路感染水平和尿液免疫反应阳性尿路感染情况。根据肾功能将患者分为Ccr>70ml/min组、Ccr<70ml/min组和Ccr+30ml/min组。三组糖尿病患者血浆免疫反应性UII水平均高于正常对照组(P&lt;0.05)。Ⅲ组患者血浆免疫反应性UII水平(15.9+/-2.2fmol/ml,平均值+/-2.2fmol/ml,n=6)较I组(10.9+/-0.9fmol/ml,n=17)和第11组(10.8+/-0.8fmol/ml,n=25)高约1.6倍(P&lt;0.05)。与对照组、I组和II组相比,III组患者尿液中更活跃的UII排泄量(52.4+/-14.8pmol/天)显著增加(P&lt;0.005)。随着肾功能的降低,免疫反应性UII的排泄分数显著增加。糖尿病视网膜病变或神经病变的存在对血浆免疫反应性UII水平和尿液免疫反应性UII排泄的影响可以忽略不计。反相高效液相色谱分析显示,正常血浆提取物中有三个免疫反应峰,正常尿液提取物中有多个免疫反应峰。因此,2型糖尿病本身是血浆免疫反应性UII水平升高的一个因素,合并肾功能衰竭是2型糖尿病患者血浆中更活跃的UII水平升高的另一个独立因素。2型糖尿病合并晚期糖尿病肾病患者尿液免疫反应性UII排泄增加可能不仅是由于血浆免疫反应性UII水平升高,而且可能是由于病变肾脏UII产生增加和/或UII降解减少。(C)2004 Elsevier Inc.保留所有权利。
Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In order to clarify the pathophysiological role of UII in diabetes mellitus, we examined plasma immunoreactive UII levels and urinary excretion of immumoreactive UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to the renal function: Group I with Ccr greater than or equal to 70 ml/min, group II with 30 less than or equal to Ccr < 70 ml/min and group III with Ccr < 30 ml/min. Plasma immumoreactive UII levels were elevated in the three diabetic groups compared with normal controls (P < 0.05). Group III patients had significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean +/- S.E.M., n = 6) by approximately 1.6-fold than did group I (10.9 +/- 0.9 fmol/ml, n = 17) and group 11 (10.8 +/- 0.8 fmol/ml, n = 25) (P < 0.05). Urinary excretion of inummoreactive UII was significantly increased in group III patients (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects, groups I and II (P < 0.005). Fractional excretion of immunoreactive UII significantly increased as renal function decreased. Presence of diabetic retinopathy or neuropathy had negligible effects on plasma immunoreactive UII levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses showed three immunoreactive peaks in normal plasma extracts and multiple immumoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus itself is a factor to elevate plasma immunoreactive UII levels, and accompanying renal failure is another independent factor for the increased plasma inummoreactive UII levels in Type 2 diabetic patients. Increased urinary immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic nephropathy may be due not only to the elevated plasma immunoreactive UII levels but also to increased UII production and/or decreased UII degradation in the diseased kidney. (C) 2004 Elsevier Inc. All rights reserved.