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脂肪細胞における肥満遺伝子とインスリン作用関連遺伝子の制御機構の研究

Research Project

Project/Area Number 09671053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NISHIMURA Haruo  Kyoto Univsity, Clinical Science and Medicine, Assistant Prof., 医学研究科, 助手 (40281729)

Co-Investigator(Kenkyū-buntansha) HOSODA Kiminori  Kyoto Univsity, Environmetal Study, Assistant Prof., 人間環境学研究科, 助手 (40271598)
YOSHIMASA Yasunao  Kyoto Univsity, Clinical Science and Medicine, Lecturer, 医学研究科, 講師 (00252437)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsLeptin / Thiazolidinedione / Insulin Action / Adipocyte / Skeletal Muscle / Obesity / インスリン / イソプロテレノール / レプチン受容体 / GLUT4 / TSH / 糖輸送担体
Research Abstract

(1) Effect of thiazolidinediones on leptin production and insulin action in rat adipocytes. Thiazolidinedione, an insulin sensitizer, reduced protein and mRNA levels of leptin in rat adipocytes after 24 hours. This compound also increased 2-deoxyglucose uptake in the adipocytes. However, mRNA level of leptin and insulin action were not changed, when the adipocytes were incubated with exogenous leptin for 24 hours, Thus it is suggested that exogenous leptin dose not affect the primary culture of adipocytes directly.
(2) Effect of leptin on insulin action in culture of skeletal muscle Leptin did not affect the insulin action including insulinsignaling systems and glucose uptake in culture of skeletal muscles (L6 cells).
(3) Insulin action in leptin transgenic mouse Leptin transgenic mouse showed no accumulation of adipocytes, both white and brown adipocytes. In vivo insulin action determined by intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) showed enhanced insulin sensitivity in the transgenic mice. It is suggested that leptin has lipoatrophic effect on adipocytes and insulin action, and that insulin action is enhanced Through central nervous systems by leptin.
(4) Concentration of plasma leptin in human There were correlations between plasma leptin and % fat , body mass index significantly. And the was also gender difference in leptin concentration (male<female). However aging did not affect the concentration. We also found some polymorphisms in leptin gene, but there were no relation between leptin and the polymorphisms in Japanese obese subjects.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Azuma N, Yoshimasa Y, Nishimura H, et al.: "The significance of the Trp64Arg mutation of the B3-adrenergic receptor gene in impaired glucose tolerance, non-insulin -dependent diabetes mellitus and insulin resistance in Japanese subjects." Metabollsm. 47. 456-460 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yonemitsu Y, Shintani M, Nishimura H, et al.: "Effect of Leptin and Troglitazone on Glucose Uptake in L6 Myotcytes." Diabetes. 47. 272A (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shintani M, Nishimura H,Yonemits S, et al.: "Differential Regulation of Free Fatty Acid and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 47. 319A (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuda J, Hosoda K, Nishimura H, et al.: "Increased adipose expression of uncoupling protein-3 gene by thizolidinediones in Wister fatty rats and in cultured adipocytes." Diabetes. 47. 1809-1814 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuzaki H, Nishimura H, Yoshimasa Y, et al.: "Nonadipose tissue production of leptin : leptin as a novel placenta-derived hormone in humans." Nature Medicine. 3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuoka N, Nishimura H, Yoshimasa Y, et al.: "Human leptin receptor gene in obese Japanese subjects : evidence against either obesity-causing mutations or association of sequence variants with obesity." Diabetologia. 40. 1204-1210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishimura H,Shintani M,Yamamoto Y,Suga J,Tanaka T,Takaya K,Yoshimasa Y,Nakao K.: "Leptin Decreases Protein and mRNA Levels of GLUT4 in Rat Adipocytes." Diabetes. 46. 59A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shintani M,Nishimura H,Yamamoto Y,Suga J,Tanaka T,Hanaoka I,Yoshimasa Y,Nishi S,Nakao K.: "Differential Regulation of Isoproterenol and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 46. 86A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Azuma N,Nishimura H,Yamamoto Y,Suga J,Shigemoto M,Nishi S,Yoshimasa Y.: "Significance of the Trp64Arg Mutation of 3-Adrenergic Receptor Gene in Insulin Resistance." Diabetes. 46. 168A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuzaki H,Ogawa Y,Hosoda K,Miyawaki T,Hanaoka I,Hiraoka J,Yasuno A,Nishimura H,Yoshimasa Y,Nishi S,Nakao K.: "Glucocorticoid regulation of leptin synthesis and secretion in humans : elevated plasma leptin levels in Cushing's syndrome." J Clin Endocrinol Metab. 82. 2542-2547 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuzaki H,Ogawa Y,Sagawa N,Hosoda K,Matsumoto T,Mise H,Nishimura H,Yoshimasa Y,Tanaka I,Mori T,Nakao K.: "Nonadipose tissue production of leptin : leptin as a novel placenta-derived hormone in humans." Nat Med. 3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuoka N,Ogawa Y,Hosoda K,Matsuda J,Masuzaki H,Miyawaki T,Azuma N,Natsui K,Nishimura H,Yoshimasa Y,Nishi S,Thompson DB,Nakao K.: "Human leptin receptor gene in obese Japanese subjects : evidence against either obesity-causing mutations or association of sequence variants with obesity." Diabetologia. 40. 1204-1210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigemoto M,Nishi S,Ogawa Y,Isse N,Matsuoka N,Tanaka T,Azuma N,Masuzaki H,Nishimura H,Yoshimasa Y,Hosoda K,Nakao K.: "Molecular screening of both th epromoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus (NIDDM)." Eur J Endocrinol. 137. 511-513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuda J,Hosoda K,Itoh H,Son C,Doi K,Tanaka T,Fukunaga Y,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Nakao K.: "Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs : their gene expression in rats fed high-fat diet." FEBS Lett. 418. 200-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Azuma N,Yoshimasa Y,Nishimura H,Yamamoto Y,Masuzaki H,Suga J,Shigemoto M,Matsuoka N,Tanaka T,Sattoh N,Igaki T,Miyamoto Y,Itoh H,Yoshimasa T,Hosoda K,Nishi S,Nakao K.: "The significance of the Trp64Arg mutation of the B3-adrenergic receptor gene in impaired glucose tolerance, non-insulin-dependent diabetes mellitus and insulin resistance in Japanese subjects." Metabolism. 47. 456-460 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yonemitsu Y,Shintani M,Yamamoto Y,Matsuoka N,Suga J,Hosoda K,Yoshimasa Y,Nishimura H.: "Effect of Leptin and Troglitazone on Glucose Uptake in L6 Myotcytes." Diabetes. 47. A272 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shintani M,Nishimura H,Yonemits S,Hosoda K,Hiraoka J,Matsuoka N,Yoshimasa Y,Nishi S,Nakao K.: "Differential Regulation of Free Fatty Acid and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 47. 319A (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuda J,Hosoda K,Itoh H,Son C,Doi K,Hanaoka I,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Odaka H,Nakao K.: "Increased adipose expression of uncoupling protein-3 gene by thizolidinediones in Wister fatty rats and in cultured adipocytes." Diabetes. 47. 1809-1814 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, T,Hosoda K,Itoh H,Son C,Doi K,Hanaoka I,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Odaka H,Nakao K.: Diabetologia. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Azuma N,Yoshimasa Y,Nishimura H,et al.: "The significance of the Trp64Arg mutation of the B3-adrenergic receptor gene in impaired glucose tolerance,non-insulin-dependent diabetes mellitus and insulin resistance in Japanese subjects." Metabollsm. 47. 456-460 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yonemitsu Y,Shintani M,Nishimura H,et al.: "Effect of Leptin and Troglitazone on Glucose Uptake in L6 Myotcytes." Diabetes. 47. 272A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shintani M,Nishimura H,Yonemits S,et al.: "Differential Regulation of Free Fatty Acid and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 47. 319A (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuda J,Hosoda K,Nishimura H,et al.: "Increased adipose expression of uncoupling protein-3 gene by thizolidinediones in Wister fatty rats and in cultured adipocytes." Diabetes. 47. 1809-1814 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishimura Haruo: "Leptin Decreases Protein and mRNA Levels of GLUT4 in Rat Adipocytes." Diabetes. 46. 59A- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shintani Matsuyo: "Differential Regulation of Isoproterenol and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 46. 86A- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masuzaki Hiroaki: "Glucocorticoid regulation of leptin synthesis and secretion in humans : elevated plasma leptin levels in Cushing's syndrome." J.Clin.Endocrinol.Metab.82. 2542-2547 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masuzaki Hiroaki: "Nonadipose tissue production of leptin : leptin as a novel placenta-derived hormone in humans." Nature Medicine. 3. 1029-1033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsuoka Naoki: "Human leptin receptor gene obese Japanese subjects : evidence against either obesity-causing mutations or association of sequence variants with cbesity." Diabetologia. 40. 1204-1210 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shigemoto Michika: "Molecilar screening of both the promoter and the protein coding regions in the human ob gene in Japanese obses subjects with non-insulin-dependent diabets mellitus (NIDDM)." Eur.J.Endocrinol.137. 511-513 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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