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Study for pathological significance of insulin-like growth factor binding proteins.

Research Project

Project/Area Number 06671058
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionTokyo Women's Medical College

Principal Investigator

HIZUKA Naomi  Tokyo Women's Medical College, Department of Medicine, Associate Professor, 医学部, 助教授 (80147397)

Co-Investigator(Kenkyū-buntansha) FUKUDA Izumi  Tokyo Women's Medical College, Department of Medicine, Clinical Associate, 医学部, 助手 (80238477)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsinsulin-like growth factor (IGF) / insulin-like growth factor binding protein (IGFBP) / インスリン様成長因子 / インスリン様成長因子結合蛋白 / (IGF) / (IGFBP)
Research Abstract

Insulin-like growth factors (IGFs) bind to specific binding proteins (IGFBPs), and it has been speculated that the IGFBPs might modulate IGF action. In this study, we have investigated pathological significance of IGFBPs as follows. 1) Pathophysiological roles of IGFBP-6 have not been elucidated. Recently we measured serum IGFBP-6 by Western immunoblot (WIB), and have found that serum IGFBP-6 levels are not GH dependent and increase in patients with chronic renal failure (CRF). In the present study, to investigate further clinical significance and regulation of serum IGFBP-6, we measured serum IGFBP-6 levels in patients with CRF after renal transplantation. Furthermore, we also measured IGFBP-2 levels. Serum IGFBP-2 and -6 levels remarkably increased in all patients with CRF.The levels did not change after hemodialysis. Serum IGFBP-6 levels dramatically decreased 1 day after renal transplantation and decreased further with the improvement of renal function. In contrast to IGFBP-6, seru … More m IGFBP-2 levels did not decrease during 14 days after renal transplantation. In addition, we demonstrated IGFBP-6 in urine. These data indicate that IGFBP-6 might be excreted by the kidneys and serum IGFBP-6 levels might be related with renal function, and that regulation of serum IGFBP-6 levels are different from that of IGFBP-2.2) Serum levels of IGFBP-2 and IGFBP-3 in cord sera were higher and lower than those in adult sera. Serum levels of IGFBP-2 in cord sera inversely correlated with birth weight and the levels of free from of IGFs. The birth weight positively correlated with serum IGF-I,and free form of IGFs. These findings suggest that changes in IGFBP-2 in fetal sera might modulate the relative concentrations of free IGFs, supposed to be active from of IGFs, and then modulate fetal growth. 3) It has been hypothesized that IGFBP-1 play a role in counter regulation of blood glucose. We found that serum IGFBP-1 did not increase in 3h after insulin-induced hypoglycemia. Therefore, we could not support the hypothesis. 4) It has been reported that IGFBPs were regulated by various agents in osteoblast-like cells, but these data were different among species. In the present study, we took advantage of cultured human osteoblasts obtained from trabecular bone, and undertook a study of effect of various agents. The cultured human osteoblasts secreted IGFBPs, mainly IGFBP-3, -4, and -2.1,25-(OH)_2D_3 inhibited the proliferation of osteoblasts, and increased osteocalcin in the media. 1,25-(OH)_2D_3 increased IGFBP-3 and slightly IGFBP-4. E_2 did not affect on the cell proliferation and osteocalcin in the media, but, increased IGFBP-3, -4 and -2. These data demonstrate that IGFBPs of human osteoblasts are regulated by effectors of bone metabolism. However, it remains to be elucidated how IGFBPs modulate IGF action in bone metabolism. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yashiro T et al.: "Increased activity of Insalin-like growth factor binding protein in human thyroid papillary cancer tissue" Jpn J Cancer Res. 85. 46-52 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukuda I et al.: "Circulating forms of insulin-like growth factor II(IGF-II) in patients with non-islet cell tumor hypogly cemia" Endocrinol Metab. 1. 89-95 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 福田いずみ,肥塚直美: "膵外腫瘍に伴う低血糖" 内分泌糖尿病科. 1. 210-215 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshida T. et al.: "Growth hormone(GH)secretory dynamics in a case of acromegalic gigantion associated with hyper prolactinemia:Noupulsatile secretion of GH maytuduce eleuated insulin-like groeth poctor-I(IGF-I)and IGF-binding proteins-3 levels" J chin Endocrinol metab. 81. 310-313 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hizuka N et al.: "Hypoglycemic effect of IGF-II is acted through mainly insulin and/or IGF-I receptor but not IGF-II receptor" Clinical Pediatric Endocrinology. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hizuka N et al.: "Current Directions in Insulin-Like Growth Factor Research" Plenum, (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yashiro T,Arai M,Shizume K,Obara T,Murakami H,Hizuka N,Emoto N,Miyakawa M,Ito K,Tsushima T: "Increased activity of insulin-like growth factor binding protein in human thyroid papillary cancer tissue." Jpn J Cancer Res. 85. 46-52 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sanaka T,Shinobe M,Ando M,Hizuka N,Kawaguchi H,Nihei H: "IGF-I as an early indicator of malnutrition in patients with end-stage renal disease." Nephron. 67. 73-81 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Horiuchi T,Shinohara Y,Sakamoto Y,Hizuka N,Watabe T,Mokuda O,Tanaka k, Shimizu N,Sugano I,Nagao K: "Expression of insuli-like growth factor II by a gastric carcinoma associated with hypoglycemia" Virchow Archiv. 42 : 4. 449-452 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukuda I,Hizuka N,Takano K,Asakawa-Yasumoto K,Okubo Y,Shimojoh, Shizume K,Demura H: "Circulating forms of insulin-like growth factor II (IGF-II) in patients with non-islet cell tumor hypoglycemia" Endocrinol Metab. 1. 89-95 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukuda I,Hizuka N,Takano K,Okubo Y,Asakawa-Yasumoto K,Shimojoh, Suzuki T,Shizume K,Demura H: "Serum insulin-like growth factor binding protein-6 (IGFBP-6) levels in various clinical conditions" Clinical Pediatric Endocrinology. 3. 171-172 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshida T,Shimatsu A,Sakane N,Hizuka N,Horikawa R,Tanaka T: "Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia : Nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels." J Clin Endocrinol metab. 81. 310-313 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hizuka N,Asakawa-Yasumoto, Takano K,Fukuda I,Okubo Y,Kazuma T,Demura H,Shizume K,Marumoto Y,Sakano K: "Hypoglycemic effect of IGF-II is acted through mainly insulin and/or IGF-I receptor but not IGF-II receptor." Clinical Pediatric Endocrinology. (in Press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hizuka N,Takano K,Asakawa-Yasumoto K,Fukuda I,Suzuki T,Demura H,Shimojoh C and Shizume K: Effects of insulin-like growth factor I (IGF-I) administrations on serum IGF binding proteins (IGFBPs) in patients with growth hormone deficiency. In : Current Directions in Insulin-Like Growth Factor Research, D LeRoith and MK Raizada eds. Plenum, New York, 301-309 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 福田いずみ,肥塚直美: "膵外腫瘍に伴う低血糖" 内分泌糖尿病科. 1. 210-215 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 肥塚直美: "IGFの構造と生理作用" 内分泌糖尿病科. 1. 441-448 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshida T et al.: "Growth hormone (GH) secretory dynamic in a case of acromegalic gigantism associated with byperprolactinemia: Naupulsatile secretion of GH may lnduce elevated insulin-like growth factor-I (IGF-I) and IGF-binding proteins-3 levels" J clin Endocrinol metab.81. 310-313 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hizuka N et al.: "Hypoglycemic effect of IGF-II is acted through mainly insulin and/or IGF-I receptor but not IGF-II receptor" Clinical Pediatric Endocrinology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukuda I,et al.: "Circulating forms of IGF-II in Patients with non-islet cell fumor hypoglycemia" Endocrinol Metab. 1. 89-95 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Horiuchi et al.: "Expression of IGF-II by a gastric carcinoma associated with hypoglycemia." Virchow Archiv. 42. 449-452 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hizuka N.et al.: "Effect of IGF-I administrations on serum IGFBPs in patients with growth thormore deficiency." Advances in Experimental Medicine and Biology. 343. 301-309 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yashiro T.et al.: "Increased activity of IGFBP in human thyroid papillary cancer tissue." Jpn J Cancer Res. 85. 46-52 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sanaka T.et al.: "IGF-I as an early indicator of malnutrition in patients with end-stage venel dise." Nephron. 67. 73-81 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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