The Role of Crosstalk between ChREBP and Clock-related genes in the Development of Metabolic syndrome

• Project/Area Number: 22590973
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gifu University
• Principal Investigator: IIZUKA Katsumi 岐阜大学, 医学部附属病院, 講師 (40431712)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Jun 岐阜大学, 大学院医学系研究科, 教授 (40270855) ; HORIKAWA Yukio 岐阜大学, 医学部附属病院, 准教授 (10323370)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: メタボリックシンドローム / ChREBP / 概日リズム / 時計遺伝子 / KLF-10 / グルカゴン受容体 / PPARα / LRH-1 / LRH－１ / SHP / 活動量 / 摂餌量 / 脂肪合成 / 脂肪分解 / 褐色脂肪細胞 / ChREBP標的遺伝子 / glucagon receptor / KLF10 / glucagon / lipogenesis / Klf-10 / de novo lipogenesis / Mlx / ChoRE

Research Abstract

We studied the role of crosstalk between carbohydrate-responsive element-binding protein (ChREBP) and clock-related genes (Klf-10 and Ppara) in the development of metabolic syndrome. Use of the feedback loop between ChREBP and clock-related genes is a common method for regulating both metabolic pathways and the circadian rhythm. Considering disorders in both metabolism and circadian rhythm coexist in metabolic syndrome, suppression of ChREBP transactivities will be beneficial in preventing metabolic syndrome.

Research Products

• [Journal Article] Liraglutide normalised glucose tolerance and the insulin response to glucose in a non- obese patient with newly diagnosed type 2 diabetes mellitus (2014)
  • Author(s): Iizuka K, Niwa H, Takahashi Y, Takeda J
  • Journal Title: Diabetol Int Volume: (In press) Issue: 4 Pages: 254-259
  • DOI: 10.1007/s13340-014-0167-x
  • Peer Reviewed
• [Journal Article] Protamine-containing insulin but not analog insulin and duration of insulin use are risk factors for the production of insulin autoantibodies in insulin-treated patients with diabetes mellitus (2014)
  • Author(s): Nishimura H, Iizuka K, Takeda J
  • Journal Title: Endocrine Journal Volume: 61 Issue: 6 Pages: 635-640
  • DOI: 10.1507/endocrj.EJ13-0544
  • NAID: 130004770454
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] LRH-1 heterozygous knockout mice are prone to mild obesity (2014)
  • Author(s): Hattori T, Iizuka K, Horikawa Y, Takeda J
  • Journal Title: Endocrine Journal Volume: 61 Issue: 5 Pages: 471-480
  • DOI: 10.1507/endocrj.EJ14-0017
  • NAID: 130004443971
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Feedback looping between ChREBP and PPARα in the regulation of lipid metabolism in brown adipose tissues (2013)
  • Author(s): Iizuka K, Wu W, Horikawa Y, Saitio M and Takeda J
  • Journal Title: Endocrine Journal Volume: 60 Issue: 10 Pages: 1145-1153
  • DOI: 10.1507/endocrj.EJ13-0079
  • NAID: 130004770387
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] グルカゴン受容体とグルコースによる発現調節-転写因子ChREBP を介した経路 (2013)
  • Author(s): 飯塚 勝美、武田 純
  • Journal Title: 生体の科学 Volume: 64(5) Pages: 406-407
• [Journal Article] Recent progress on the role of ChREBP in glucose and lipid metabolism [Review] (2013)
  • Author(s): Iizuka K
  • Journal Title: Endocrine Journal Volume: 60 Issue: 5 Pages: 543-555
  • DOI: 10.1507/endocrj.EJ13-0121
  • NAID: 10031184521
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Role of glucose-6-phosphate and xylulose-5-phosphate in the regulation of glucose-stimulated gene expression in the pancreatic β cell line, INS-1E (2013)
  • Author(s): K. Iizuka
  • Journal Title: Endocrine Journal Volume: 60 Issue: 4 Pages: 473-482
  • DOI: 10.1507/endocrj.EJ12-0413
  • NAID: 10031170636
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] グルカゴン受容体とグルコースによる発現調節 転写因子ChREBPを介した経路 (2013)
  • Author(s): 飯塚勝美 武田純
  • Journal Title: 生体の科学 Volume: 64(5) Pages: 406-407
• [Journal Article] Recent progress on the role of ChREBP in glucose and lipid metabolism. (2013)
  • Author(s): Iizuka K
  • Journal Title: Endocrine Journal Volume: in press
  • NAID: 10031184521
  • Peer Reviewed
• [Journal Article] Hepatic FoxO1 Integrates Glucose Utilization and Lipid Synthesis through Regulation of Chrebp O-Glycosylation (2012)
  • Author(s): Ido-Kitamura Y, Sasaki T, Kobayashi M, Kim HJ, Lee YS, Kikuchi O, Yokota-Hashimoto H, Iizuka K, Accili D, Kitamura T
  • Journal Title: PLoS One Volume: 7 Issue: 10 Pages: e47231-e47231
  • DOI: 10.1371/journal.pone.0047231
  • Peer Reviewed
• [Journal Article] A case of glycemic instability and insulin allergy due to anti-insulin antibodies in a patient with type 2 diabetes (2012)
  • Author(s): Iizuka K, Tomita R, Horikawa Y, Takeda J
  • Journal Title: Diabetol Int Volume: 3 Issue: 4 Pages: 233-238
  • DOI: 10.1007/s13340-012-0077-8
  • NAID: 10030590194
  • Peer Reviewed
• [Journal Article] Effectiveness of the glucagon test in estimating islet function for liraglutide treatment in a lean diabetic patient with impaired insulin response to glucose: a case report (2012)
  • Author(s): Iizuka K, Tomita R, Horikawa Y, Takeda J
  • Journal Title: Diabetol Int Volume: 3 Issue: 2 Pages: 103-108
  • DOI: 10.1007/s13340-012-0068-9
  • Peer Reviewed
• [Journal Article] Normalization of fasting hyperglycemia is beneficial for successful introduction of small amount of the GLP-1 analog liraglutide in an obese patient with type 2 diabetes mellitus (2012)
  • Author(s): Iizuka K, Tomita R, Suwa T, Horikawa Y, Takeda J
  • Journal Title: Diabetol Int Volume: 3 Issue: 1 Pages: 61-64
  • DOI: 10.1007/s13340-011-0052-9
  • NAID: 40019209011
  • Peer Reviewed
• [Journal Article] Rat glucagon receptor mRNA is directly regulated by glucose through transactivation of the carbohydrate response element binding protein (2012)
  • Author(s): Iizuka K, Tomita R, Takeda J, Horikawa Y
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Issue: 4 Pages: 1107-1112
  • DOI: 10.1016/j.bbrc.2011.12.042
  • Peer Reviewed
• [Journal Article] Krüppel-like factor-10 is directly regulated by carbohydrate response element-binding protein in rat primary hepatocytes (2011)
  • Author(s): Iizuka K, Takeda J, Horikawa Y
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 4 Pages: 638-643
  • DOI: 10.1016/j.bbrc.2011.08.016
  • Peer Reviewed
• [Journal Article] その他の転写因子(ChREBP ほか)とその役割 (2011)
  • Author(s): 飯塚 勝美
  • Journal Title: 日本臨床 Volume: 69(S1)
• [Journal Article] Synergistic effect of α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment (2011)
  • Author(s): Horikawa Y, Enya M, Iizuka K, Chen GY, Kawachi S, Suwa T, Takeda J
  • Journal Title: J Diabet Invest Volume: 2 Issue: 3 Pages: 200-203
  • DOI: 10.1111/j.2040-1124.2010.00081.x
  • Peer Reviewed
• [Journal Article] DPP-4阻害薬とGLP-1受容体作動薬の使い分けとポジショニング (2011)
  • Author(s): 飯塚勝美, 堀川幸男, 武田純
  • Journal Title: Prog.Med. Volume: 31 Pages: 1421-1425
• [Journal Article] その他の転写因子(ChREBPほか)とその役割 (2011)
  • Author(s): 飯塚勝美
  • Journal Title: 日本臨床増刊号 メタボリックシンドローム(第2版) Volume: 69 Pages: 275-278
• [Journal Article] Synergistic effect of -glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment (2011)
  • Author(s): Yukio Horikawa, Mayumi Enya, Katsumi Iizuka, Gui Ying Chen, Shin-ichi Kawachi, Tetsuya Suwa, Jun Takeda
  • Journal Title: Journal of Diabetes Investigation Volume: (印刷中,印刷中)
  • Peer Reviewed
• [Presentation] Role of ChREBP and PPARa in the regulation of glucose and lipid metabolism in brown adipocytes (2013)
  • Author(s): Iizuka K, Wu W, Hattori T, Horikawa Y, Saito M, Takeda J
  • Organizer: 49th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Barcelona, Spain
• [Presentation] Crosstalk between ChREBP and PPARα in brown adipocytes lipid metabolism American Diabetes Association's (2013)
  • Author(s): Iizuka K, Wu W, Tsuchida H, Hattori T, Horikawa Y, Saito M, Takeda J
  • Organizer: 73th Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
• [Presentation] 褐色脂肪細胞におけるChREBPとPPARαの機能関連についての検討 (2013)
  • Author(s): 飯塚勝美、呉烏德勒胡、土田宏美、服部泰輔、堀川幸男、斉藤昌之、武田 純
  • Organizer: 第56回 日本糖尿病学会 年次学術集会
  • Place of Presentation: 熊本
• [Presentation] LRH-1の肥満病態における意義 -ob/ob LRH-1ダブルノックアウトマウスを用いた解析- (2013)
  • Author(s): 服部 泰輔、飯塚 勝美、呉 烏徳勒胡、土田 宏美、堀川 幸男、武田 純
  • Organizer: 第56回 日本糖尿病学会 年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 血中osteonectin濃度に影響を及ぼす因子の検索 (2013)
  • Author(s): 呉 烏徳勒胡、飯塚 勝美、土田 宏美、服部 泰輔、堀川 幸男、武田 純
  • Organizer: 第56回 日本糖尿病学会 年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Crosstalk between ChREBP and PPARα in brown adipocytes lipid metabolism (2013)
  • Author(s): Katsumi Iizuka, Wudelehu Wu, Hiromi Tsuchida, Taisuke Hattori, Yukio Horikawa1, Masayuki Saito, Jun Takeda
  • Organizer: American Diabetes Association’s 73th Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Role of ChREBP and PPARa in the regulation of glucose and lipid metabolism in brown adipocytes (2013)
  • Author(s): Katsumi Iizuka, Wudelehu Wu, Taisuke Hattori, Yukio Horikawa, Masayuki Saito, Jun Takeda
  • Organizer: 20. 49th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Barcelona, Spain
• [Presentation] Crosstalk between ChREBP and PPARalpha in Brown Adipocytes Lipid Metabolism (2013)
  • Author(s): Iizuka K
  • Organizer: American Diabetes Association 73th Scientific session
  • Place of Presentation: Chicago, USA
• [Presentation] 褐色脂肪細胞におけるChREBPとPPARαの機能連関についての検討 (2013)
  • Author(s): 飯塚勝美
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市、熊本県
• [Presentation] Glucagon Receptor and Glucagon-like Peptide-1 Receptor mRNA Expression are Inversely Regulated by Glucose Through ChREBP Activation (2012)
  • Author(s): Iizuka K,Tomita R,Horikawa Y,Takeda J
  • Organizer: American Diabetes Association's 72th Scientific Sessions
  • Place of Presentation: Philadelphia, PA
• [Presentation] Deletion of the small heterodimer partner gene protects against fatty liver and dyslipidemia, but not obesity and glucose intolerance in C57BL/6J mice fed a high-fat diet (2012)
  • Author(s): Iizuka K, Wu W, Tomita R, Tsuchida H, Horikawa Y,Takeda J
  • Organizer: 48th EASD Annual Meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] Glucagon receptor and incretin receptors are inversely regulated by glucose through ChREBP activation (2012)
  • Author(s): Iizuka K,Tomita R,Wu W, Horikawa Y, Takeda J
  • Organizer: the 9th IDF-WPR Congress&4th AASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
• [Presentation] Glucagon Receptor and Glucagon-like Peptide-1 Receptor mRNA Expression are Inversely Regulated by Glucose Through ChREBP Activation (2012)
  • Author(s): Iizuka K
  • Organizer: American Diabetes Association 72th Scientific session
  • Place of Presentation: Philadelphia, USA
• [Presentation] Deletion of the small heterodimer partner gene protects against fatty liver and dyslipidemia, but not obesity and glucose intolerance in C57BL/6J mice fed a high-fat diet (2012)
  • Author(s): Iizuka K
  • Organizer: 48th EASD annual meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] Glucagon receptor and incretin receptors are inversely regulated by glucose through ChREBP activation. (2012)
  • Author(s): Iizuka K
  • Organizer: "the 9th IDF-WPR Congress & 4th AASD Scientific Meeting"
  • Place of Presentation: Kyoto, Japan
• [Presentation] GLP1アナログ（Liraglutide)導入時における空腹時血糖正常化の有用性 膵島機能およびAdipokineに注目した検討 (2012)
  • Author(s): 飯塚勝美
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜市、神奈川県
• [Presentation] LRH-1(Liver Receptor homologue-1)ヘテロノックアウトマウスは摂餌量増加により体重増加をきたす。 (2012)
  • Author(s): 服部泰輔
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜市、神奈川県
• [Presentation] グルコース活性化転写因子ChREBPの転写活性調節におけるグルコース６リン酸とキシルロース5リン酸の役割 (2012)
  • Author(s): 飯塚勝美
  • Organizer: 第85回日本内分泌学会年次学術集会
  • Place of Presentation: 名古屋市、愛知県
• [Presentation] (ワークショップ血糖管理・β細胞)GLP-1アナログ導入時の空腹血糖正常 (2011)
  • Author(s): 飯塚勝美、冨田礼子、堀川幸男、武田純
  • Organizer: 日本糖尿病合併症学会年次学術集会
  • Place of Presentation: 埼玉県さいたま市
  • Year and Date: 2011-10-14
• [Presentation] Role of glucose-6-phosphate in regulation of glucose-stimulated gene expression in the pancreatic beta cell line INS-1E (2011)
  • Author(s): Iizuka K, Tomita R, Horikawa Y, Takeda J
  • Organizer: 47^<th> annual Meeting of the Eurpean Association for the Study of Diabetes (EASD)
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2011-09-15
• [Presentation] Rat Krueppel like factor 10 (Klf-10) gene expression is regulated by the carbohy drate response element binding protein ChREBP in primary rat hepatocytes (2011)
  • Author(s): Iizuka K, Horikawa Y, Tomita R, Suwa T, Takeda J
  • Organizer: 71th Scientific sessions of American Diabetes Association (ADA)
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2011-06-26
• [Presentation] 脂肪合成遺伝子発現調節機構におけるグルコース感受性転写因子ChREBPと時計遺伝子Klf-10の機能連関に関する検討 (2011)
  • Author(s): 飯塚勝美、堀川幸男、土田宏美, 冨田礼子、服部泰輔、塩谷真由美, 武田純
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2011-05-21
• [Presentation] グルコース感受性転写因子ChREBPに注目した膵島におけるグルコース依存性遺伝子発現調節機構の解明 (2011)
  • Author(s): 西村英尚、飯塚勝美、冨田礼子, 堀川幸男、武田純
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2011-05-20
• [Presentation] 当院にて経験したインスリン抗体陽性糖尿病4症例の検討 (2011)
  • Author(s): 冨田礼子、飯塚勝美, 諏訪哲也、堀川幸男、武田純
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2011-05-19
• [Presentation] 高脂肪食負荷Liver Receptor Homolog1 (LRH_1)ヘテロノックアウトマウスの代謝学的解析 (2011)
  • Author(s): 服部泰輔、飯塚勝美、堀川幸男
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2011-05-19
• [Presentation] グルコース活性化転写因子ChREBPに注目した時計関連遺伝子KLF10遺伝子のグルコース誘導性発現調節機構の解明 (2011)
  • Author(s): 飯塚勝美、堀川幸男、土田宏美, 服部泰輔、冨田礼子、塩谷真由美, 諏訪哲也、武田純
  • Organizer: 第84回日本内分泌学会年次学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2011-04-21
• [Presentation] 高脂肪食負荷LRH-1ヘテロノックアウトマウスの代謝学的解析 (2011)
  • Author(s): 服部泰輔、飯塚勝美、土田宏美, 青松元昭、冨田礼子、諏訪哲也, 武田純
  • Organizer: 第84回日本内分泌学会年次学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2011-04-21
• [Presentation] Role of glucose-6-phosphate in the regulation of glucose stimulated gene expression in the pancreatic beta cell line INS-1E (2011)
  • Author(s): Iizuka K,Tomita R,Horikawa Y,Takeda J
  • Organizer: 47th EASD Annual Meeting
  • Place of Presentation: Lisbon, Portugal
• [Presentation] Rat Krueppel-Like Factor 10 (Klf-10) Gene Expression Is Regulated by the Carbohydrate Response Element Binding Protein ChREBP in Primary Rat Hepatocytes (2011)
  • Author(s): Iizuka K, Horikawa Y,Tomita R,Suwa T,Takeda J
  • Organizer: American Diabetes Association's 71st Scientific Sessions
  • Place of Presentation: San Diego, California
• [Presentation] Fibroblast growth factor 21(FGF21)はラット初代肝細胞においてグルコース活性化転写因子ChREBPにより誘導される (2010)
  • Author(s): 飯塚勝美、堀川幸男、服部泰輔、青松元昭、塩谷真由美、土田宏美、陳桂英、武田純
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2010-05-27
• [Presentation] α-グルコシダーゼ阻害薬とDPP4阻害薬によるCombination Therapy (2010)
  • Author(s): 堀川幸男、塩谷真由美、川地慎一、飯塚勝美、諏訪哲也、武田純
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2010-05-27
• [Presentation] 2型糖尿病発症におけるインクレチン関連遺伝子多型の影響について (2010)
  • Author(s): 塩谷真由美、堀川幸男、飯塚勝美、武田純
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2010-05-27
• [Book] Chapter 7 - The Feedforward and Feedback Loop between ChREBP and its Target Genes in the Regulation of Glucose and Lipid Metabolism (2013)
  • Author(s): Iizuka K
  • Publisher: Leon V. Berhardt, Nova Science Publishers, (Editors: Leon V)
• [Book] Advances in Medicine and Biology Volume 63 (Leon V. Berhardt editor) (2013)
  • Author(s): Iizuka K
  • Total Pages: 222
  • Publisher: Nova Science Publishers