Molecular mechanism of diabetes mellitus based on beta-cell transcription factor network

• Project/Area Number: 25293212
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: Yamagata Kazuya 熊本大学, 大学院生命科学研究部, 教授 (70324770)
• Co-Investigator(Kenkyū-buntansha): Yoshizawa Tatsuya 熊本大学, 大学院生命科学研究部, 准教授 (40313530) ; Sato Yoshifumi 熊本大学, 大学院生命科学研究部, 助教 (90622598) ; 門松 毅 熊本大学, 大学院生命科学研究部, 助教 (90555757)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 糖尿病 / インスリン分泌 / 転写因子 / MODY / HNF / インスリン / グルコキナーゼ

Outline of Final Research Achievements

Mutations in the genes encoding hepatocyte nuclear factor (HNF) cause impaired insulin secretion and diabetes mellitus. However, the detailed molecular mechanisms are largely unknown. In the present work, we found that Crp is a direct target gene of HNF1 and high sensitive could be a biomarker for HNF1 diabetes. In addition, we found that Tmed6 is a target gene of HNF1. Furthermore, we identified that Anks4b, a direct target of HNF4, regulates insulin secretion by beta-cells.

Research Products

• [Journal Article] Role of SIRT7 in hepatic lipid metabolism (2015)
  • Author(s): Yamagata K.
  • Journal Title: Diabetology International Volume: 6 Issue: 3 Pages: 193-196
  • DOI: 10.1007/s13340-015-0226-y
  • NAID: 40020601082
  • Peer Reviewed
• [Journal Article] High resolution imaging of intracellular oxygen concentration by phosphorescence lifetime (2015)
  • Author(s): Kurokawa H, Ito H, Inoue M, Tabata K, Sato Y, Yamagata K, Kizaka-Kondoh S, Kadonosono T, Yano S, Kamachi T.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 10657-10657
  • DOI: 10.1038/srep10657
  • Peer Reviewed / Open Access
• [Journal Article] RNA interference-mediated knockdown of Smad1 inhibits receptor activator of nuclear factor κB ligand expression induced by BMP-2 in primary osteoblasts. (2015)
  • Author(s): Yoshikawa Y, Yoshizawa T, Domae E, Hieda Y, Takeyama A, Hirota S, Kawamoto A, Goda S, Tamura I, Kamada A, Komasa Y, Morita S, Yamagata K, Ikeo T.
  • Journal Title: Archives of Oral Biology Volume: 60 Issue: 9 Pages: 1319-26
  • DOI: 10.1016/j.archoralbio.2015.06.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway (2015)
  • Author(s): Araki S, Izumiya Y, Rokutanda T, Ianni A, Hanatani S, Kimura Y, Onoue Y, Senokuchi T, Yoshizawa T, Yasuda O, Koitabashi N, Kurabayashi M, Braun T, Bober E, Yamagata K, Ogawa H
  • Journal Title: Circulation Volume: 132(12) Issue: 12 Pages: 1081-1093
  • DOI: 10.1161/circulationaha.114.014821
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Roles of hepatic glucokinase in intertissue metabolic communication: examination of novel liver-specific glucokinase knockout mice (2015)
  • Author(s): Hayashi H
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 3 Pages: 727-732
  • DOI: 10.1016/j.bbrc.2015.03.097
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway. (2014)
  • Author(s): Yoshizawa T, Karim Md. F, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Kakeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K.
  • Journal Title: Cell Metab. Volume: 9 Issue: 4 Pages: 712-721
  • DOI: 10.1016/j.cmet.2014.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Moderate hypoxia induces beta-cell dysfunction with HIF-1alpha independent gene expression changes (2014)
  • Author(s): Sato Y
  • Journal Title: PLOS ONE Volume: 9 Issue: 12 Pages: e114868-e114868
  • DOI: 10.1371/journal.pone.0114868
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Low serum level of high-sensitivity C-reactive protein in a Japanese subject with MODY3 (2014)
  • Author(s): Ohki T, Utsu Y, Morita S, Karim M.F., Sato Y, Yoshizawa T, Yamamura K, Yamada K, Kasayama S, Yamagata K
  • Journal Title: J. Diabetes Invest Volume: (in press) Pages: 407-423
  • DOI: 10.1016/b978-0-12-800174-5.00016-8
  • Peer Reviewed
• [Journal Article] Early postprandial glucagon surge affects postprandial glucose levels in obese and non-obese patients with type 2 diabetes (2013)
  • Author(s): Kozawa J et al.
  • Journal Title: Endocrine Journal Volume: 60 Issue: 6 Pages: 813-818
  • DOI: 10.1507/endocrj.EJ13-0018
  • NAID: 10031184551
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Inhibition of H3K18 deacetylation of SIRT7 by Myb-binding protein la (Mybbpla) (2013)
  • Author(s): Karim Md F, Yoshizawa T, Sato Y, Sawa T, Tomizawa K, A kaike T and Yamagata K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 441 Issue: 1 Pages: 157-163
  • DOI: 10.1016/j.bbrc.2013.10.020
  • Peer Reviewed
• [Presentation] Hypoxia reduces HNF4a/MODY1 protein expression of pancreatic b-cells (2015)
  • Author(s): Yamagata K.
  • Organizer: Keystone symposia
  • Place of Presentation: Kyoto
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] 新規MODY3モデルマウスの作製：ICRバックグラウンドHnf1aノックアウトマウス (2015)
  • Author(s): 羽根田昌樹
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口市
  • Year and Date: 2015-05-21
• [Presentation] b細胞低酸素による転写因子HNF4a蛋白発現低下機序の検討 (2015)
  • Author(s): 佐藤叔史
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口市
  • Year and Date: 2015-05-21
• [Presentation] SIRT7による糖脂質代謝制御 (2015)
  • Author(s): 吉澤達也
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口市
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] SIRT7による糖脂質代謝制御 (2014)
  • Author(s): 山縣和也
  • Organizer: 第３５回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] Sirt7遺伝子欠損マウスは、高脂肪食負荷による糖尿病・脂肪肝・肥満に抵抗性である (2014)
  • Author(s): 吉澤達也
  • Organizer: 第５７回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 膵β細胞低酸素による転写因子発現低下メカニズムの検討 (2014)
  • Author(s): 佐藤叔史
  • Organizer: 第５７回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 膵β細胞におけるHNF4alpha標的遺伝子Anks4bの機能解析 (2014)
  • Author(s): 作永真由美
  • Organizer: 第５７回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Hypoxic stress and pancreatic beta-cell dysfunction (2014)
  • Author(s): Kazuya Yamagata
  • Organizer: 第５７回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Hypoxic stress and pancreatic beta-cell dysfunction (2013)
  • Author(s): Kazuya Yamagata
  • Organizer: 第５６回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本・メルパルク熊本
• [Presentation] 軽度低酸素による膵β細胞障害機構の検討 (2013)
  • Author(s): 佐藤叔史、井上正宏、山縣和也
  • Organizer: 第５６回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本・熊本市現代美術館
• [Presentation] 軽度低酸素による膵β細胞障害機構の検討 (2013)
  • Author(s): 佐藤叔史、井上正宏、山縣和也
  • Organizer: 第３６回日本分子生物学会年会
  • Place of Presentation: 神戸・神戸ポートアイランド
• [Presentation] 核内因子による糖脂質代謝制御
  • Author(s): 山縣和也
  • Organizer: 平成２５年度大阪糖尿病アカデミー特別講演
  • Place of Presentation: 大阪・グランビア大阪
  • Invited
• [Remarks] 熊本大学大学院生命科学研究部 病態生化学分野
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/biochem2/biochem2.html
• [Remarks] 熊本大学大学院生命科学研究部 病態生化学分野
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/biochem2/biochem2.html