成人GH分泌不全症をモデルとした非アルコール性脂肪性肝炎の病態解明と治療法の開発
Project/Area Number |
20390262
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Kobe University |
Principal Investigator |
CHIHARA Kazuo Kobe University, 医学研究科, 客員教授 (00107955)
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Co-Investigator(Kenkyū-buntansha) |
高橋 裕 神戸大学, 医学研究科, 講師 (70301281)
飯田 啓二 神戸大学, 医学研究科, 医学研究員 (80324911)
|
Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2009: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
Keywords | 内分泌学 / 成人GH分泌不全症 / 非アルコール性脂肪性肝炎 / 成長ホルモン / 脂肪肝 / NASH |
Research Abstract |
Adult growth hormone deficiency (AGHD) is characterized by visceral obesity, abnormal lipid profile, and liver dysfunction. In this study, we clarified that in AGHD, the prevalence of NAFLD/NASH was substantially increased. We also demonstrated that GH exerts its effect mainly via IGF-I and IGF-I ameliorates mitochondrial dysfunction, oxidative stress, and abnormal activation of stellate cells, which leads to fibrosis in the liver. These results indicate that GH and IGF-I play an important role in liver and are closely related with the pathogenesis of NASH.
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Report
(4 results)
Research Products
(130 results)
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[Journal Article] Reactive oxygen species play an essential role in IGF-I signaling and IGF-I-induced myocyte hypertrophy in C2C12 myocytes.2011
Author(s)
Handayaningsih AE, Iguchi G, Fukuoka H, Nishizawa H, Takahashi M, Yamamoto M, Herningtyas EH, Okimura Y, Kaji H, Chihara K, Seino S, Takahashi Y
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Journal Title
Related Report
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[Journal Article] Branched-chain amino acids protect against dexamethasone-induced soleus muscle atrophy in rats.2010
Author(s)
Yamamoto D, Maki T, Herningtyas EH, Ikeshita N, Shibahara H, Sugiyama Y, Nakanishi S, Iida K, Iguchi G, Takahashi Y, Kaji H, Chihara K, Okimura Y
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Journal Title
Muscle Nerve. 41(6)
Pages: 819-827
Related Report
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[Journal Article] IGF-I stimulates reactive oxygen species (ROS) production and inhibits insulin-dependent glucose uptake via ROS in 3T3-L1 adipocytes.2010
Author(s)
Fukuoka H, Iida K, Nishizawa H, Imanaka M, Takeno R, Iguchi G, Takahashi M, Okimura Y, Kaji H, Chihara K, Takahashi Y
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Journal Title
Growth Horm IGF Res 20(3)
Pages: 212-219
Related Report
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[Journal Article] W194XProp1 and S156insTProp1, both of which have intact DNA-binding domain, show a different DNA-binding activity to the Prop1-binding element in human Pit-1 gene.2010
Author(s)
Shibahara H, Ikeshita N, Sugiyama Y, Toda K, Yamamoto D, Herningtyas EH, Maki T, Kubota E, Iguchi G, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y
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Journal Title
Mol Cell Endocrinol 323(2)
Pages: 167-171
NAID
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[Journal Article] Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans.2010
Author(s)
Yamamoto M, Iguchi G, Takeno R, Okimura Y, Sano T, Takahashi M, Nishizawa H, Handayaningshi AE, Fukuoka H, Tobita M, Saitoh T, Tojo K, Mokubo A, Morinobu A, Iida K, Kaji H, Seino S, Chihara K, Takahashi Y
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Journal Title
J Clin Invest 121(1)
Pages: 113-119
NAID
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[Journal Article] IGF-I stimulates reactive oxygen species(ROS)production and inhibits insulin dependent glucose uptake via ROS in 3T3-L1 adipocytes2010
Author(s)
Fukuoka H, Iida K, Nishizawa H, Imanaka M, Takeno R, Iguchi G, Takahashi M, Okimura Y, Kaji H, Chihara K, Takahashi Y
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Journal Title
Growth Hormone and IGF-I Research (In press, 掲載確定)
Related Report
Peer Reviewed
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[Journal Article] Branched-chain amino acids protect against dexamethasone-induced soleus muscle atrophy in rats2010
Author(s)
Yamamoto D, Maki T, Herningtyas EH, Ikeshita N, Shibahara H, Sugiyama Y, Nakanishi S, Iida K, Iguchi G, Takahashi Y, Kaji H, Chihara K, Okimura Y
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Journal Title
Muscle Nerve (In press, 掲載確定)
Related Report
Peer Reviewed
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[Journal Article] GHRP-2,a GHS-R agonist,directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1.2008
Author(s)
D Yamamoto, N Ikeshita, T Matsubara, H Tasaki, E Henny Herningtyas, K Toda, K Iida, Y Takahashi, H Kaji, K Chihara, Y Okimura
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Journal Title
Life Sciences 82
Pages: 460-466
Related Report
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[Journal Article] Low Serum IGF-I/GH Ratio Is Associated with Abnormal Glucose Tolerance in Acromegaly.2008
Author(s)
H Fukuoka, Y Takahashi, K Iida, T Kudo, H Nishizawa, M Imanaka, R Takeno, G Iguchi, K Takahashi, Y Okimura, H Kaji, K Chihara
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Journal Title
Hormone Research 69
Pages: 165-171
Related Report
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[Journal Article] Identification and Analysis of Prophet of Pit-1-Binding Sites in Human Pit-1 Gene.2008
Author(s)
N Ikeshita, M Kawagishi, H Shibahara, K Toda, T Yamashita, D Yamamoto, Y Sugiyama, G Iguchi, K Iida, Y Takahashi, H Kaji, K Chihara, Y Okimura
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Journal Title
Endocrinology 149(11)
Pages: 5491-5499
Related Report
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[Journal Article] Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes.2008
Author(s)
M.Takahashi, Y.Takahashi, K.Takahashi, F.N.Zolotaryov, K.S.Hong, R.Kitazawa, K.Iida, Y.Okimura, H.Kaji, S.Kitazawa, M.Kasuga, K.Chihara
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Journal Title
FEBS Lett 582(5)
Pages: 573-578
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[Journal Article] Hepatic failure and enhanced oxidative stress in mitochondrial diabetes.2008
Author(s)
Y.Takahashi, K.Iida, R.Takeno, R.Kitazawa, S.Kitazawa, H.Kitamura, Y.Fujioka, H.Yamada, F.Kanda, S.Ohta, K.Nishimaki, M.Fujimoto, T.Kondo, G.Iguchi, K.Takahashi, H.Kaji, Y.Okimura, K.Chihara
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Journal Title
Endocr J 55(3)
Pages: 509-514
NAID
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[Presentation] Sirt1 negatively regulates IGF-I production by growth hormone in hepatocytes.2010
Author(s)
M.Yamamoto, G.Iguchi, H.Fukuoka, M.Takahashi, H.Nishizawa, E.Handayaningsih, Y.Okimura, H.Kaji, K.Chihara, S.Seino, Y.Takahashi
Organizer
5th International Congress of the GRS and the IGF Society
Place of Presentation
New York, NY, USA.(Sheraton New York Hotel & Towers)
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[Presentation] 健常成人における体格指数、ウエスト周囲径と血中IGF-1 SDスコア2009
Author(s)
島津章, 千原和夫, 肥塚直美, 寺本明, 田中敏章, 巽圭太, 立花克彦, 勝又規行, 横谷進, 藤枝憲二, 大磯ユタカ
Organizer
第82回日本内分泌学会学術総会
Place of Presentation
群馬県民会館、前橋商工会議所(群馬県)
Related Report
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[Presentation] IGF-IはNASHモデルマウスの耐糖能および肝線維化を改善する2009
Author(s)
西沢衡, 飯田啓二, 吉岡嗣朗, 高橋健太郎, 高橋路子, 山本雅昭, 村脇あゆみ, 井口元三, 置村康彦, 加治秀介, 清野進, 千原和夫, 高橋裕
Organizer
第82回日本内分泌学会学術総会
Place of Presentation
群馬県民会館、前橋商工会議所(群馬県)
Related Report
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[Presentation] Reactive oxygen species play an essential role in IGF-I signaling and its biological action2009
Author(s)
Handayaningsih Evi, 福岡秀規, 西沢衡, 高橋路子, 山本雅昭, Herningtyas Henny, 置村康彦, 加治秀介, 清野進, 千原和夫, 高橋裕
Organizer
第82回日本内分泌学会学術総会
Place of Presentation
群馬県民会館、前橋商工会議所(群馬県)
Related Report
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