PLASMA LEVELS OF UROTENSIN II AND ITS URINARY EXCRETION IN PATIENTS WITH DIABETES MELLITUS : RELATION WITH DIABETIC NEPHROPATHY

糖尿病患者血浆中尾加压素 II 水平及其尿排泄：与糖尿病肾病的关系

• 批准号: 13671094
• 负责人: TOTSUNE Kazuhito
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671094/
• 关键词: urotensin II; endothelin; angiotensin II; renalfailure; diabetes mellitus; hypertension; heart failure; gene expression; 遺伝子多型; アンジオテンシンII

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. The potency of the vasoconstriction of UII is an order of magnitude greater than that of endothelin-1 and angiotensin II. In order to clarify the pathophysiological role of UII in the progression of organ damages, we examined plasma UII levels, urinary excretion of UII, and mRNA expression of UII in various organs.Results:1.We newly developed a radioimmunoassay specific to human UII, and examined plasma UII levels in patients with various diseases. Plasma UII levels were elevated in patients with chronic renal failure (Lancet 2001). Patients with type-2 diabetes mellitus also had elevated plasma UII levels (Clin Sci 2003). Urinary examination showed that diabetes itself was a factor to elevate plasma UII levels and the renal failure, not proteinuria, was another isolated factor to increase plasma UII levels (Peptides 2004 (in press)). Patients with heart failure and those with hypertension secondary to endocrine diseases such as pheochromocytoma, primary aldosteronism and Cushing syndrome also had increased plasma UII levels.2.UII mRNA was expressed not only in brain but also in the various peripheral organs of humans and rats.3.We examined UII mRNA expression in hearts and kidneys of rats with 5/6 renal mass ablation or acute myocardial infarction after coronary ligation.4.Expression of UII mRNA in cultured human endothelial cells was increased by hypoxia, suggesting that UII has an important roles the progression of renal ischemic injury.5.UII has a proliferative effect on cultured human tumor cell lines (Clin Sci 2002).

尾加压素II（UII）是迄今发现的最强的血管收缩肽。UII的血管收缩效力比内皮素-1和血管紧张素II大一个数量级。为了阐明UII在器官损伤进展中的病理生理作用，我们检测了血浆UII水平、尿UII排泄量和各器官UII mRNA表达。结果：1.我们新开发了一种特异于人UII的放射免疫分析法，并检测了各种疾病患者的血浆UII水平。慢性肾衰竭患者的血浆UII水平升高（Lancet 2001）。2型糖尿病患者的血浆UII水平也升高（Clin Sci 2003）。尿液检查显示，糖尿病本身是升高血浆UII水平的一个因素，肾衰竭（而非蛋白尿）是升高血浆UII水平的另一个孤立因素（Peptides 2004（出版中））。心力衰竭患者和继发于嗜铬细胞瘤等内分泌疾病的高血压患者，原发性醛固酮增多症和库欣综合征的血浆UII水平也升高。2. UII mRNA不仅在大脑中表达，而且在人类和大鼠的各种外周器官中也有表达。3.我们检测了5/10 6.缺氧可增加培养的人内皮细胞UII mRNA的表达，提示UII在肾缺血性损伤的进展中具有重要作用。5. UII对培养的人肿瘤细胞系具有增殖作用（Clin Sci 2002）。

项目成果

Kazuhiro Takahashi: "Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin : expression and effects on proliferation"Clin Sci (Lond). 103 Suppl48. 35S-38S (2002)

Kazuhiro Takahashi：“三种血管活性肽，内皮素-1，肾上腺髓质素和尾加压素-II，在不同来源的人类肿瘤细胞系中：表达和对增殖的影响”Clin Sci（伦敦）。

Totsune K, Takahashi K, Murakami O et al.: "Increased plasma urotensin II levels in patients with diabetes melltus"Clin Sci(London). 104(1). 1-5 (2003)

Totsune K、Takahashi K、Murakami O 等人：“糖尿病患者血浆尾加压素 II 水平升高”Clin Sci（伦敦）。

Kazuhito Totsune: "Role of urotensin II in patients on dialysis."Lancet. 358. 810-811 (2001)

Kazuhito Totsune：“尾加压素 II 在透析患者中​​的作用。”柳叶刀。

Kazuhiro Takahashi: "Three vasoactive peptides, endothelin-1, adreno medullin and urotensin-II, in human tumour cell lines of different origin : expression and effects on proliferation."Clin Sci(Lond).. 103(Suppl48). S35-S38 (2002)

Kazuhiro Takahashi：“三种血管活性肽，内皮素-1，肾上腺髓质素和尾加压素-II，在不同来源的人类肿瘤细胞系中：表达及其对增殖的影响。”Clin Sci（伦敦）.. 103（Suppl48）。

Nakabayashi M, Takahashi K, Totsune K, Sasano H, et al.: "Orexin-A expression in human peripheral tissues"Mol Cell Endocrinology. 205. 43-50 (2003)

Nakabayashi M、Takahashi K、Totsune K、Sasano H 等：“人外周组织中的 Orexin-A 表达”Mol 细胞内分泌学。