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

Research Project

Project/Area Number 13671094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTohoku University

Principal Investigator

TOTSUNE Kazuhito  Tohoku University, Graduate School of Pharmaceutical Science and Medicine, Associate Professor, 大学院・薬学研究科, 助教授 (10217515)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Kazuhiro  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80241628)
MURAKAMI Osamu  Tohoku University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (00157744)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsurotensin 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
Research Abstract

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).

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhiro Takahashi: "Expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in a human renal cell carcinoma cell line, VMRC-RCW."Clin Exp Nephrol.. 5. 246-249 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhito Totsune: "Increased plasma urotensin II levels in patients with diabetes mellitus."Clin Sci(Lond).. 104. 1-5 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhiro Takahashi: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II."Peptides.. 24. 301-306 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhito Totsune: "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."Peptides.. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhito Totsune: "Role of urotensin Ii in patients on dialysis"Lancet. 358. 810-811 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhiro Takahashi: "Expression of three vasoactive peptides, urotensin-II, adrenomedullin and endothelin-1, in a human renal cell carcinoma cell line, VMRC-RCW"Clin Exp Nephrol.. 5. 246-249 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhito Totsune: "Increased plasma urotensin II levels in patients with diabetes mellitus"Clin Sci (Lond). 104. 1-5 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhiro Takahashi: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II"Peptides. 24. 301-306 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhito Totsune: "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"Peptides. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi K, Udono R, Totsune K, Murakami O, Shibahara S.: "Suppression of cytokine-induced expression of adrenomedullin and endothelin-1 by dexamethasone in T98G human glioblastoma cells"Peptides. 24. 1053-1062 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Li Y, Totsune K, Takeda K, Furuyama K, Shibahara S, Takahashi K.: "Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha"European J of Endocrinology. 149. 231-238 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakabayashi M, Takahashi K, Totsune K, Sasano H, et al.: "Orexin-A expression in human peripheral tissues"Mol Cell Endocrinology. 205. 43-50 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi K, Totsune K, Murakami O, Shibahara S, et al.: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II"Peptides. 24. 301-306 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Udono-Fujimori R, Totsune K, Shibahara S, Takahashi K, et al.: "Adrenomedullin in the eye"Regulatory Peptide. 112. 95-101 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Totsune K, Takahashi K, Arihara Z, Sone M, Ito S, Murakami O.: "Increased plasma urotensin II levels in patients with diabetes mellitus"Clinical Science (London). 104. 1-5 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Li Y, Totsune K, Takahashi K et al.: "Decreased expression of adrenomedullin during adipocyte-differentiation of 3T3-L1 cells"Hypertens Res. Suppl 26. S41-S44 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi K, Totsune K, Murakami O.: "Adrenocortical peptides : autocrine or paracrine regulators for the steroid hormon secretion or the cell proliferation?"Exp Clin Endocrinol Diabetes. 110(8). 373-380 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi K, Totsune K, Murakami O. et al.: "Three vasoactive pepbides, endothelin-1,adrenomedullin and urotensin-II, in humantumor cell lines of different origin : expression and effects on proliferation"Clin Sci (London). Suppl 48. S35-S38 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi K, Totsune K, Murakami O. et al.: "Expression of prolactin-releasing peptide and its receptor in the human adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas and neuroblastomas"Peptides. 23(6). 1135-1140 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura Y, Takahashi K, Totsune K, et al.: "Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart"J Clin Endocrinol Metab. 87(1). 340-346 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi K, Totsune K, Murakami O: "Expression of three vasoactive peptides, urotensin-II, adrenomedullin and endothelin-1, in human renal cell carcinoma cell line, VMRC-RCW"Clin Exp Nephrol. 5. 246-249 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Totsune K, Takahashi K, Brenner BM, et al.: "Adrenomedullin and its receptor complexes in remnant kidneys of rats with renal mass ablation : decreased expression of calcitonin receptor-like receptor and receptor-activity modifying protein-3"Peptides. 22(11). 1933-1937 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitamuro T, Takahashi K, Totsune K, et al.: "Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein (RAMP) 2 during hypoxia in cultured human neuroblastoma cells"Peptides. 22(11). 1795-1801 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Totsune K, Takahashi K, Murakami O, et al.: "Role of urotensin II in patients on dialysis"Lancet. 358. 810-811 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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