Development of animal model for the blood sugar regulation by glycosphingolipids and study on the molecular pathogenesis of inflammation in adipose tissue

• Project/Area Number: 24500495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nagoya City University
• Principal Investigator: MIYOSHI ICHIRO 名古屋市立大学, 医学(系)研究科(研究院), 教授 (10183972)
• Co-Investigator(Kenkyū-buntansha): OKAMURA Tadashi 独立行政法人国立国際医療研究センター, その他部局等, 実験動物管理室長 (00333790)
• Co-Investigator(Renkei-kenkyūsha): KITAMURA Hiroshi 酪農学園大学, 獣医学部, 教授 (80312403)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 疾患モデル / スフィンゴ糖脂質 / 血糖調節 / 遺伝子組換えマウス / 脂肪組織

Outline of Final Research Achievements

We attempted to elucidate the involvement of the glycosphingolipids in the blood sugar level regulation by comparison analysis of the pathological condition of glucosylceramide synthase(Ugcg) gene-manipulated mice fed with high-fat diet. The body weight gain was drastic in KoHe mice expressing lower Ugcg activity, but retarded in TgM mice expressing higher Ugcg activity. KoHe showed insulin resistance and hyperinsulinemia with hypertrophy and hyperplasia of　pancreatic islet and　severe accumulation of lipid and glycogen in liver. On the contrary, apparent impairment in insulin secretion was demonstrated in TgM. KoHe and TgM is useful model for obese diabetes and non-obese diabetes, respectively.

Research Products

• [Journal Article] Colony-StimulatingFactor-1 Signaling Suppresses Renal Crystal Formation. (2015)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Kitamura Hiroshi, Yasui Takahiro, Naiki Taku, Hamamoto Shuzo, Ando Ryosuke, Mizuno Kentaro, Kawai Noriyasu, Tozawa Keiichi, Asano Kenichi, Tanaka Masato, Miyoshi Ichiro, Kohri Kenjiro
  • Journal Title: Journal of the American Society of Nephrology Volume: 25 Issue: 8 Pages: 1680-1697
  • DOI: 10.1681/asn.2013060675
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Modified autonomic regulation in mice mutated in the ß4 subunit of the lh/lh calcium channel. (2015)
  • Author(s): Murakami M, Suzuki T, Wu TW, Kuwasako K, Takahashi E, Watanabe H, Murakami AM, Miyoshi I, Yanagisawa T, Sasano H, Ono K, Ohba T
  • Journal Title: Biochem Biophys Res Commun Volume: pii: S0006-291X(15) Issue: 2 Pages: 200-205
  • DOI: 10.1016/j.bbrc.2015.03.112
  • Peer Reviewed / Open Access
• [Journal Article] A novel transgenic mouse model carrying human Tribbles related protein 3 (TRB3) gene and its site specific phenotype. (2014)
  • Author(s): Sakai Y, Fukamachi K, Futakuchi M, Miyoshi I, Tsuda H, Suzui M, Hayashi H
  • Journal Title: Biol Pharm Bull Volume: 37(6) Pages: 1068-1074
  • NAID: 130004147355
  • Peer Reviewed
• [Journal Article] A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. (2014)
  • Author(s): Sherman-Baust CA, Kuhn E, Valle BL, Shih IeM, Kurman RJ, Wang TL, Amano T, Ko MS, Miyoshi I, Araki Y, Lehrmann E, Zhang Y, Becker KG, Morin PJ
  • Journal Title: J Pathol Volume: 233(3) Issue: 3 Pages: 228-237
  • DOI: 10.1002/path.4353
  • Peer Reviewed
• [Journal Article] Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue (2013)
  • Author(s): Kitamura H, Naoe Y, Kimura S, Miyamoto T, Okamoto S, Toda C, Shimamoto Y, Iwanaga T, Miyoshi I
  • Journal Title: Adipocyte Volume: 2 Issue: 4 Pages: 227-236
  • DOI: 10.4161/adip.25608
  • Peer Reviewed
• [Journal Article] Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. (2013)
  • Author(s): Kitamura et al.
  • Journal Title: FASEB J. Volume: 27 Issue: 12 Pages: 4940-4953
  • DOI: 10.1096/fj.13-233528
  • Peer Reviewed
• [Journal Article] Improvement of spontaneous alternation behavior deficit by activation of α4β2 nicotinic acetylcholine receptor signaling in the ganglioside GM3-deficient mice. (2013)
  • Author(s): Niimi K, Nishioka C, Miyamoto T, Takahashi E, Miyoshi I, Itakura C, Yamashita T.
  • Journal Title: Biomed Res. Volume: 34(4) Pages: 189-195
  • Peer Reviewed
• [Journal Article] Targeted disruption of fad24, a regulator of adipogenesis, causes pre-implantation embryonic lethality due to the growth defect at the blastocyst stage. (2013)
  • Author(s): Ochiai N, Nishizuka M, Miyamoto T, Miyoshi I, Ikawa M, Osada S, Imagawa M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 438(2) Issue: 2 Pages: 301-305
  • DOI: 10.1016/j.bbrc.2013.07.061
  • Peer Reviewed
• [Journal Article] Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes (2013)
  • Author(s): Okamura, T., Pei, XY., Miyoshi, I., Shimizu, Y., Takanashi-Yanobu, R., Mototani, Y., Takao Kanai, T., Satoh, J., Kimura, N. and Kasai, N
  • Journal Title: J Diabetes Res Volume: 2013 Pages: 986462-986462
  • DOI: 10.1155/2013/986462
  • Peer Reviewed
• [Journal Article] Exclusive expression of VMAT2 in noradrenergic neurons increases viability of homozygous VMAT2 knockout mice (2013)
  • Author(s): Ohara A, Kasahara Y, Yamamoto H, Hata H, Kobayashi H, Numachi Y, Miyoshi I, Hall FS, Uhl GR, Ikeda K, Sora I
  • Journal Title: Biochem Biophys Res Commun Volume: 432 Issue: 3 Pages: 526-532
  • DOI: 10.1016/j.bbrc.2013.02.014
  • Peer Reviewed
• [Presentation] 名古屋での11年11ヶ月間 (2015)
  • Author(s): 三好一郎
  • Organizer: 日本技術者協会東北支部総会
  • Place of Presentation: 東北大学（宮城県）
  • Year and Date: 2015-04-04
  • Invited
• [Presentation] マクロファージの USP2 - 新たな糖尿病制御 分子 - (2014)
  • Author(s): 北村浩，木村俊介，岡部潤，宮本智美，嶋本良則，直江吉則，戸田智得，岡本士毅，三好一郎
  • Organizer: 日本実験動物医学会シンポジウム（第157回日本獣医学会学術集会）
  • Place of Presentation: 北海道大学（北海道）
  • Year and Date: 2014-09-10
• [Presentation] Zinc Finger Nucleases (ZFNs)を用いたノックアウトマウスの作製 (2014)
  • Author(s): 宮本智美，三好一郎
  • Organizer: 第85回東海実験動物研究会
  • Place of Presentation: 名古屋市立大学（愛知県）
  • Year and Date: 2014-08-30
• [Presentation] マクロファージのＵＳＰ２による２型糖尿病制御の可能性 (2014)
  • Author(s): 北村浩，木村俊介，岡部潤，宮本智美，嶋本良則，直江吉則，戸田智得，岡本士毅，三好一郎
  • Organizer: 第61回日本実験動物学会総会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2014-05-15 – 2014-05-17
• [Presentation] マクロファージ分子M-modによる肥満症・糖尿病の制御 (2013)
  • Author(s): 北村 浩、木村 俊介、嶋本 良則、岡部 潤、宮本 智美 、直江 吉則、 岡本 士毅、戸田 知得、Assam El-Osta、三好 一郎
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学（岐阜県）
• [Presentation] ob/obマウスの２型糖尿病進行に対するプロポリスの抑制効果-腸管膜脂肪組織における免疫細胞の役割- (2013)
  • Author(s): 北村 浩、直江吉則、木村俊介、宮本智美、三好一郎
  • Organizer: 第８３回東海実験動物研究会
  • Place of Presentation: 名古屋市立大学（愛知県）
• [Presentation] Roles of a macrophage molecule M-mod in type 2 diabetes. (2012)
  • Author(s): Kitamura H, Ito M, Kimura S, Shimamoto Y, Miyamoto T, Watarai H, Okabe J, Iwanaga T, Ohara O, Miyoshi I
  • Organizer: Experimental Biology 2012.
  • Place of Presentation: San Diego Convention Center (San Diego, USA)
• [Presentation] Possible involvement of a novel macrophage molecule in pathogenesis of type 2 diabetes. (2012)
  • Author(s): Kitamura H, Ohara O, Kimura S, Miyamoto T, Ito M, Shimamoto Y, Naoe Y, Okabe J, Hase Ｋ，Watarai H, Miyoshi I
  • Organizer: The 4th EMBO meeting
  • Place of Presentation: Nice Acropolis Convention Center (Nice, France)
• [Book] 発生工学．獣医学教育モデル･コア･カリキュラム準拠 実験動物学．久和茂（編）. (2013)
  • Author(s): 三好一郎
  • Publisher: 朝倉書店
• [Remarks] 遺伝子改変マウスを用いた膜スフィンゴ糖脂質の機能解析
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/project.html
• [Remarks] マクロファージに発現する新しい機能分子と疾患の関係
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/project.html
• [Remarks] 遺伝子改変マウスを用いた膜スフィンゴ糖脂質の機能解析
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/project.html
• [Remarks] マクロファージに発現する新しい機能分子と疾患の関係
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/project.html
• [Remarks] 遺伝子改変マウスを用いた膜スフィンゴ糖脂質の機能解析
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/project.html