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Elucidation of development and improvement of leptin resistance

Research Project

Project/Area Number 23791054
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Endocrinology
Research InstitutionKyoto University

Principal Investigator

KUSAKABE Toru  京都大学, 医学研究科, 助教 (60452356)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsレプチン / レプチン抵抗性 / アミリン / GLP-1 / 肥満 / AMPK / 異所性脂肪蓄積 / インスリン抵抗性
Research Abstract

Coadministration of leptin and exenatide significantly reduced food intake and body weight in obese type2 diabetic mice, compared with either monotherapy alone. Moreover, coadministration of leptin and exenatide normalized blood glucose levels accompanied by improvement of insulin sensitivity, restoration of glucose stimulated insulin secretion, normalization of triglyceride contents in non-adipose tissues, improvement of plasma glucagon levels and restoration of pancreatic insulin contents, while not each monotherapy. Pair-feeding experiments indicated that exenatide enhanced the leptin’s effects through independent mechanism of caloric restriction. These findings suggest that coadministration of leptin and exenatide could be a beneficial treatment for obese type2 diabetes by eliciting leptin’s effects.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (40 results)

All 2013 2012 2011

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (34 results)

  • [Journal Article] Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.2013

    • Author(s)
      N. Yamada-Goto, G. Katsuura, K. Ebihara, M. Inuzuka, Y. Ochi, Y. Yamashita, T. Kusakabe, A. Yasoda, N. Asahara-Satoh, H. Ariyasu, K. Hosoda, K. Nakao.
    • Journal Title

      Diabetes

      Volume: 62(5) Issue: 5 Pages: 1500-1504

    • DOI

      10.2337/db12-0718

    • NAID

      120005244943

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leptin activates hepatic 5’ AMP-Activated Protein Kinase through sympathetic nervous system and α1 adrenergic receptor: A potential mechanism for improvement of fatt Li Yver in lipodystrophy by leptin2012

    • Author(s)
      Miyamoto L, Nakao K, et al
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 48 Pages: 40441-40447

    • DOI

      10.1074/jbc.m112.384545

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Premature Atherosclerosis in a Japanese Diabetic Patient with Atypical Familial Partial Lipodystrophy and Hypertriglyceridemia2012

    • Author(s)
      M. Iwanishi
    • Journal Title

      Internal Medicine

      Volume: 51 Issue: 18 Pages: 2573-2579

    • DOI

      10.2169/internalmedicine.51.7461

    • NAID

      130002062378

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional Magnetic Resonance Imaging Analysis of Food-Related Brain Activity in Patients with Lipodystrophy Undergoing Leptin Replacement Therapy2012

    • Author(s)
      Aotani D, Nakao K, et al
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 97 Issue: 10 Pages: 3663-3671

    • DOI

      10.1210/jc.2012-1872

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice2012

    • Author(s)
      N.Yamada-Goto, K.Ebihara, K.Hosoda, K.Nakao, et al
    • Journal Title

      J Neuroendocrinol

      Volume: (in press) Issue: 8 Pages: 1120-1125

    • DOI

      10.1111/j.1365-2826.2012.02327.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice2012

    • Author(s)
      T.Kusakabe, K.Ebihara, K.Nakao, et al
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 302 Issue: 8 Pages: E924-E931

    • DOI

      10.1152/ajpendo.00198.2011

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] インスリン抵抗性と異所性脂肪蓄積の関連が示唆された Werner 症候群の一例、2012

    • Author(s)
      酒井 建
    • Organizer
      第49回日本糖尿病学会近畿地方会、
    • Place of Presentation
      京都市
    • Year and Date
      2012-11-17
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満症治療におけるレプチンの可能性、2012

    • Author(s)
      海老原健
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] レプチン/GLP-1 受容体作動薬共投与による肥満 2 型糖尿病治療の有用性、2012

    • Author(s)
      酒井 建
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] Beneficial Effects of Combination Therapy With Leptin and Exenatide in a Mouse Model of Type2 Diabetes With Increased Adiposity 、2012

    • Author(s)
      酒井 建
    • Organizer
      72ndscientific sessions American Diabetes Association
    • Place of Presentation
      フィラデルフィア(アメリカ)
    • Related Report
      2012 Final Research Report
  • [Presentation] レプチン/GLP-1 受容体作動薬共投与による肥満 2 型糖尿病治療の有用性2012

    • Author(s)
      酒井 建
    • Organizer
      第55回日本糖尿病学会年次学術集会、
    • Place of Presentation
      横浜市
    • Related Report
      2012 Final Research Report
  • [Presentation] Leptin Modulates Brain Activity Associated With Feeding Behavior in Patients With Lipodystrophy 、2012

    • Author(s)
      青谷大介
    • Organizer
      19thEuropean Congress on Obesity、
    • Place of Presentation
      リヨン(フランス)
    • Related Report
      2012 Final Research Report
  • [Presentation] Leptin modulates brain neural activity associated with feeding behavior in patients with lipodystrophy2012

    • Author(s)
      青谷大介
    • Organizer
      15thInternational & 14thEuropean Congress of Endocrinology
    • Place of Presentation
      フィレンツェ(イタリア)
    • Related Report
      2012 Final Research Report
  • [Presentation] レプチン、アミリン共投与による糖脂質代謝改善に関する検討、2012

    • Author(s)
      日下部 徹
    • Organizer
      第85回日本内分泌学会学術総会、
    • Place of Presentation
      名古屋市
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満2型糖尿病に対するレプチン、アミリン共投与の有用性に関する検討、2012

    • Author(s)
      日下部 徹
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] fMRI を用いた、脂肪萎縮症の食欲異常およびレプチン治療による効果の検討2012

    • Author(s)
      青谷大介
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] Leptin Modulates Brain Activity Associated With Feeding Behavior in Patients With Lipodystrophy、2012

    • Author(s)
      青谷大介
    • Organizer
      WORKSHOP ON RARE SYNDROMIC BODY FAT DISORDERS What Can They Teach Us?
    • Place of Presentation
      ベセスダ(アメリカ)
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満2型糖尿病に対するレプチン、アミリン共投与の有用性に関する検討2012

    • Author(s)
      日下部徹
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチンを用いた非アルコール性脂肪肝治療の可能性に関する検討2012

    • Author(s)
      片岡祥子
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] fMRIを用いた、脂肪萎縮症の食欲異常およびレプチン治療による効果の検討2012

    • Author(s)
      青谷大介
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチン、アミリン共投与による糖脂質代謝改善に関する検討2012

    • Author(s)
      日下部徹
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] 遺伝子改変ラットを用いたチアゾリジンの脂肪肝に対する効果の種族差の検討2012

    • Author(s)
      阿部 恵
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of leptin deficient Lepmkyo/ Lepmkyo rat-evidence for its superiority over Lepob/ Lepob mouse as a model for human obesity2012

    • Author(s)
      M. Aizawa-Abe
    • Organizer
      15th International & 14th European Congress of Endocrinology
    • Place of Presentation
      Florence, Italy
    • Related Report
      2012 Annual Research Report
  • [Presentation] Leptin modulates brain neural activity associated with feeding behavior in patients with lipodystrophy2012

    • Author(s)
      D.Aotani
    • Organizer
      15th International & 14th European Congress of Endocrinology
    • Place of Presentation
      Florence, Italy
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of Leptin Deficient Rats-Evidence of Superiority Over Lepob/Lepob Mice as a Model For Human Obesity2012

    • Author(s)
      M. Aizawa-Abe
    • Organizer
      19th European Congress on Obesity
    • Place of Presentation
      Lyon, Frarnce
    • Related Report
      2012 Annual Research Report
  • [Presentation] Leptin Modullates Brain Activity Associated With Feeding Behavior in Patients With Lipodystrophy2012

    • Author(s)
      D.Aotani
    • Organizer
      19th European Congress on Obesity
    • Place of Presentation
      Lyon, Frarnce
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチン/GLP-1受容体作動薬共投与による肥満2型糖尿病治療の有用性2012

    • Author(s)
      酒井 建
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Benefical Effects of Combination Therapy With Leptin and Exenatide in a Mouse Model of Type2 Diabetes With Increased Adiposity2012

    • Author(s)
      T.Sakai
    • Organizer
      72nd scientific sessions American Diabetes Association
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肥満症治療におけるレプチンの可能性2012

    • Author(s)
      海老原健
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチン/GLP-1受容体作動薬共投与による肥満2型糖尿病治療の有用性2012

    • Author(s)
      酒井 建
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脂肪萎縮症原因遺伝子seipinの生体における意義に関する検討2012

    • Author(s)
      海老原千尋
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] インスリン抵抗性と異所性脂肪蓄積の関連が示唆されたWerner症候群の一例2012

    • Author(s)
      酒井 建
    • Organizer
      第49回日本糖尿病学会近畿地方会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチン補充治療開始後10年以上が経過した全身性脂肪萎縮症の1例2012

    • Author(s)
      海老原千尋
    • Organizer
      第49回日本糖尿病学会近畿地方会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] 上半身のみ脂肪萎縮を呈し糖脂質代謝異常を伴わない後天性部分性脂肪萎縮症の一例、2011

    • Author(s)
      日下部 徹
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路市
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満 2 型糖尿病におけるレプチン/エキセンディン 4 共投与の有用性、2011

    • Author(s)
      酒井 建
    • Organizer
      第32回日本肥満学会、
    • Place of Presentation
      淡路市
    • Related Report
      2012 Final Research Report
  • [Presentation] 脂肪萎縮症における食欲異常および摂食関連脳領域の神経活動に対するレプチン補充療法の効果、2011

    • Author(s)
      青谷大介
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路市
    • Related Report
      2012 Final Research Report
  • [Presentation] 脂肪萎縮性糖尿病における食欲異常および脳神経活動に対するレプチン治療の効果の解析、2011

    • Author(s)
      青谷大介
    • Organizer
      第54回日本糖尿病学会年次学術集会、
    • Place of Presentation
      札幌市
    • Related Report
      2012 Final Research Report
  • [Presentation] 脂肪萎縮症における食欲異常および脳神経活動に対するレプチン治療の効果の解析2011

    • Author(s)
      青谷大介
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      神戸市
    • Related Report
      2012 Final Research Report
  • [Presentation] 上半身のみ脂肪萎縮を呈し糖脂質代謝異常を伴わない後天性部分性脂肪萎縮症の一例2011

    • Author(s)
      日下部徹
    • Organizer
      第32回 日本肥満学会
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 肥満2型糖尿病におけるレプチン/エキセンディン4共投与の有用性2011

    • Author(s)
      酒井建
    • Organizer
      第32回 日本肥満学会
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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