Role of TBP-2 of pancreatic B cells in glucose intolerance

• Project/Area Number: 23591308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kochi University
• Principal Investigator: FUJIMOTO Shimpei 高知大学, 教育研究部医療学系, 教授 (00333576)
• Co-Investigator(Kenkyū-buntansha): INAGAKI Nobuya 京都大学, 医学研究科, 教授 (30241954)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); 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: TBP-2 / 糖尿病 / B細胞 / 膵B細胞 / TBP-２

Research Abstract

This study was designed to elucidate in vivo regulation of thioredoxin-binding protein 2 (TBP-2) and roles of TBP-2 in glucose intolerance. Disruption of TBP-2 in whole body ameliorates glucose level in ob/ob mouse, a model of obese diabetes. In B cell-specific TBP-2 transgenic mice, generated in this study, glucose tolerance was not altered, but B cell area was reduced, which suggests a role of TBP-2 in regulation of B cell mass. Treatment of ob/ob mice by hypoglycemic agents and high fat diet on normal mice reveled that hyperglycemia, not obese induced by high fat diet, plays a role in overexpression of TBP-2 in B cells in vivo.

Research Products

• [Journal Article] Palmitate induces reactive oxygen species production andβ-cell dysfunction by activating NADPH oxidase via Src signaling (2014)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato H, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Inagaki N
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 1 Pages: 19-26
  • DOI: 10.1111/jdi.12124
  • Peer Reviewed
• [Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction (2013)
  • Author(s): Sasaki M, Fujimoto S, Sato Y, Nishi Y, Mukai E, Yamano G, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N
  • Journal Title: Diabetes Volume: 62 Issue: 6 Pages: 1996-2003
  • DOI: 10.2337/db12-0903
  • Peer Reviewed
• [Journal Article] Tetrahydro biopterin has a glucose-lowering effect by suppressing hepatic gluconeogenesis in an endothelial nitric oxide synthase- dependent manner in diabetic mice (2013)
  • Author(s): Abudukadier A, Fujita Y, Obara A, Ohashi A, Fukushima T, Sato Y, Ogura M, Nakamura Y, Fujimoto S, Hosokawa M, Hasegawa H, Inagaki N
  • Journal Title: Diabetes Volume: 62 Issue: 9 Pages: 3033-3043
  • DOI: 10.2337/db12-1242
  • Peer Reviewed
• [Journal Article] Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury (2013)
  • Author(s): Ishihara M, Urushido M, Hamada K, Matsumoto T, Shimamura Y, Ogata K, Inoue K, Taniguchi Y, Horino T, Fujieda M, Terada Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 305(4) Issue: 4 Pages: 495-509
  • DOI: 10.1152/ajprenal.00642.2012
  • Peer Reviewed
• [Journal Article] 酸化ストレスと膵β細胞機能 (2013)
  • Author(s): 田原裕美子、藤本新平、稲垣暢也
  • Journal Title: Diabetes Frontier Volume: 24 Pages: 527-232
  • URL: http://www.m-review.co.jp/
• [Journal Article] Upregulation of HNF-1β during experimental acute kidney injury plays a crucial role in renal tubule regeneration. (2012)
  • Author(s): Ogata K,Inoue K,et al
  • Journal Title: 10.1152/ajprenal.00086 Volume: 303 Issue: 5 Pages: 689-699
  • DOI: 10.1152/ajprenal.00086.2012
  • Peer Reviewed
• [Journal Article] Liver X receptorαis involved in the transcriptional regulation of the 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase gene (2012)
  • Author(s): Zhao LF, Iwasaki Y, Nishiyama M, Taguchi T, Tsugita M, Okazaki M, Nakayama S, Kambayashi M, Fujimoto S, Hashimoto K, Murao K, Terada Y
  • Journal Title: Diabetes Volume: 61 Issue: 5 Pages: 1062-1071
  • DOI: 10.2337/db11-1255
  • Peer Reviewed
• [Journal Article] Role of mitochondrial phosphate carrier in metabolism-secretion coupling in rat insulinoma cell line INS-1 (2011)
  • Author(s): Nishi Y, Fujimoto S, Sasaki M, Mukai E, Sato H, Sato Y, Tahara Y, Nakamura Y, Inagaki N
  • Journal Title: Biochem J Volume: 435 Issue: 2 Pages: 421-430
  • DOI: 10.1042/bj20101708
  • Peer Reviewed
• [Journal Article] Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic βcells: a simulation study (2011)
  • Author(s): Cha CY , Nakamura Y, Himeno Y, Wang J,Fujimoto S, Inagaki N, Earm YE, Noma A
  • Journal Title: J Gen Physiol Volume: 138(1)巻 Issue: 1 Pages: 21-37
  • DOI: 10.1085/jgp.201110611
  • Peer Reviewed
• [Journal Article] Systems Analysis of GLP-1 Receptor Signaling in Pancreatic {beta}-cells (2011)
  • Author(s): Takeda Y, Amano A, Noma A, Nakamura Y, Fujimoto S, Inagaki N
  • Journal Title: Am J Physiol Cell Physiol Volume: 301(4) Issue: 4 Pages: C792-C803
  • DOI: 10.1152/ajpcell.00057.2011
  • Peer Reviewed
• [Journal Article] Role of endogenous ROS production in impaired metabolism-secretion coupling of diabetic pancreaticβcells (2011)
  • Author(s): Fujimoto S, Mukai E, Inagaki N
  • Journal Title: Prog Biophys Mol Biol Volume: 107 Issue: 2 Pages: 304-310
  • DOI: 10.1016/j.pbiomolbio.2011.07.013
  • Peer Reviewed
• [Journal Article] Molecular mechanism of impaired metabolism-secretion coupling in diabetic pancreaticβcells (2011)
  • Author(s): Fujimoto S
  • Journal Title: Diabetol Int Volume: 2 Issue: 3 Pages: 122-126
  • DOI: 10.1007/s13340-011-0040-0
• [Journal Article] Targetingβ-cell functions in therapy for type 2d iabetes (2011)
  • Author(s): Fujimoto S, Inagaki N
  • Journal Title: J Diabetes Investig Volume: 2 Issue: 3 Pages: 178-179
  • DOI: 10.1111/j.2040-1124.2011.00117.x
• [Journal Article] 2型糖尿病のインスリン分泌障害において膵β細胞の機能低下あるいはmassの減少のどちらが重要なのか? (2011)
  • Author(s): 藤本新平、稲垣暢也
  • Journal Title: 内分泌・糖尿病・代謝内科 Volume: 32 Pages: 399-401
  • NAID: 40018869236
  • URL: http://www.kahyo.com/
• [Journal Article] Exendin-4 suppresses SRC activity and reactive oxygen species production in diabetic Goto-Kakizaki rat islets in an Epac-dependent manner (2010)
  • Author(s): Mukai E, Fujimoto S, Sato H, Oneyama C, Kominato R, Sato Y, Sasaki M, Nishi Y, Okada M, Inagaki N
  • Journal Title: Diabetes Volume: 60(1) Issue: 1 Pages: 218-226
  • DOI: 10.2337/db10-0021
  • Peer Reviewed
• [Journal Article] グルコースによるインスリン分泌動態惹起経路と増幅経路
  • Author(s): 藤本新平
  • Journal Title: 日本臨床 Volume: 70増刊(最新臨床糖尿病学) Pages: 104-108
  • URL: http://www.nippon-rinsho.co.jp/
• [Presentation] Palmitate induces ROS production andβ-cell dysfunction by activating NADPH oxidase via Src signaling, American Diabetes Association (2013)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato H, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Seino Y, Inagaki N
  • Organizer: 73rd Scientific Sessions
  • Place of Presentation: Moscone Center, Chicago, IL, USA
  • Year and Date: 2013-06-23
• [Presentation] リンゴ由来プロシアニジン類による糖尿病モデルマウスにおける抗糖尿病作用の検討 (2013)
  • Author(s): 小倉かさね、藤本新平、稲垣暢也(他9名)
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本他、熊本市
  • Year and Date: 2013-05-18
• [Presentation] Srcはグルコキナーゼ活性調節を介して膵β細胞グルコース応答性インスリン分泌に関与する (2013)
  • Author(s): 佐藤広規、藤本新平、稲垣暢也(他9名)
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本他、熊本市
  • Year and Date: 2013-05-16
• [Presentation] Thioredoxin binding protein-2(TBP- 2)が膵β細胞で果たす役割についての検討 (2013)
  • Author(s): 田原裕美子、藤本新平、稲垣暢也(他9名)
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本他、熊本市
  • Year and Date: 2013-05-16
• [Presentation] Palmitate induces ROS production and β-cell dysfunction by activating NADPH oxidase via Src signaling (2013)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato H, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Seino Y, Inagaki N
  • Organizer: American Diabetes Association, 73rd Scientific Sessions
  • Place of Presentation: McCormick Place, Chicago, IL, USA
• [Presentation] Persistent reduction of ROS ameliorates metabolism-secretion coupling in cultured diabetic GK Islets by suppressing Warburg effect (2012)
  • Author(s): Sasaki M, Fujimoto S, Nishi Y, Mukai E, Yamano G, Sato Y, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N
  • Organizer: American Diabetes Association, 72nd Scientific Sessions
  • Place of Presentation: McCormick Place Convention Center, Philadelphia, PA, USA
  • Year and Date: 2012-06-10
• [Presentation] 活性酸素種抑制によるWarburg効果改善を介するGKラットインスリン分泌障害改善効果癌代謝類似代謝障害制御の重要性 (2012)
  • Author(s): 佐々木真弓、藤本新平、稲垣暢也(他8名)
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2012-05-17
• [Presentation] Persistent reduction of ROS ameliorates metabolism-secretion coupling in cultured diabetic GK Islets by suppressing Warburg effect (2012)
  • Author(s): Sasaki M, Fujimoto S, Nishi Y, Mukai E, Yamano G, Sato Y, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N
  • Organizer: American Diabetes Association, 72nd Scientific Sessions
  • Place of Presentation: McCormic Place Convention Center, Philadelphia, PA, USA
• [Presentation] Metabolic dysfunction in diabetes : Metabolic pathways at the crossroads of diabetes and cancer (2011)
  • Author(s): Fujimoto S
  • Organizer: The 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: ヒルトン東京ベイ,Tokyo, Japan
  • Year and Date: 2011-10-21
• [Presentation] Impaired insulin secretion due to mitochondrial dysfunction in diabetes (2011)
  • Author(s): Fujimoto S
  • Organizer: The 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: ヒルトン東京ベイ,Tokyo, Japan
  • Year and Date: 2011-10-21
• [Presentation] Role of endogenous ROS production in amelioration of impaired metabolism-secretion coupling of diabetesβ-cells by augmentation of GLP-1 signals (2011)
  • Author(s): Fujimoto S, Mukai E, Inagaki N
  • Organizer: Asia Islet Biology & Incretin Symposium (AIBIS) 2011
  • Place of Presentation: Crowne Plaza, Beijing, China
  • Year and Date: 2011-07-21
• [Presentation] 糖尿病における膵β細胞代謝-分泌連関障害の分子機構 (2011)
  • Author(s): 藤本新平
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: さっぽろ芸術文化の館、札幌市(受賞講演1(リリー賞))
  • Year and Date: 2011-05-19
• [Presentation] Role of endogenous ROS production in metabolism-secretion coupling of pancreaticβ-cells (2011)
  • Author(s): Fujimoto S, Mukai E, Inagaki N
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: ロイトン札幌、札幌市
  • Year and Date: 2011-05-19
• [Presentation] Impaired insulin secretion due to mitochondrial dysfunction in diabetes (2011)
  • Author(s): Fujimoto S
  • Organizer: Croucher Foundation Advance Study Institute (ASI) on"Mitochondrial Stress in Diabetes and Aging"
  • Place of Presentation: Mrs Chen Yang Foo Oi Telemedicine Centre, Hong Kong, China
  • Year and Date: 2011-04-29
• [Presentation] 平成23年度糖尿病学会賞（リリー賞）受賞講演：糖尿病における膵β細胞代謝-分泌連関障害の分子機構
  • Author(s): 藤本新平
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: さっぽろ芸術文化の館（北海道札幌市）
• [Presentation] シンポジウム(英語)：Role of endogenous ROS production in metabolism-secretion coupling of pancreatic β-cells
  • Author(s): Fujimoto S, Mukai E, Inagaki N
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
• [Presentation] Metabolic dysfunction in diabetes: Metabolic pathways at the crossroads of diabetes and cancer
  • Author(s): Fujimoto S
  • Organizer: The 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: ヒルトン東京ベイ（千葉県浦安市）
• [Presentation] Impaired insulin secretion due to mitochondrial dysfunction in diabetes
  • Author(s): Fujimoto S
  • Organizer: The 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: ヒルトン東京ベイ（千葉県浦安市）