Development of inter-organ network-mediated beta-cell mass increasing strategies

• Project/Area Number: 23591294
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tohoku University
• Principal Investigator: IMAI Junta 東北大学, 大学病院, 講師 (80431500)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 糖尿病 / 膵β細胞 / インスリン / 臓器間ネットワーク / 自律神経

Research Abstract

We tested the effects of previously reported pancreatic vagal nerve-derived peptides on proliferation of pancreatic islet cells using isolated pancreatic islets from rats and mice. We found vagal nerve derived factors to induce proliferation of pancreatic islet cells.
We also examined gene expressions of pancreatic islets from hepatic ERK- activated mice by microarray analysis, and identified the transcription factor which plays an important role in inducing proliferation of pancreatic beta-cells. In addition, we found that the activity of the transcription factor is up-regulated in isolated pancreatic islets from rats and mice stimulated by aforementioned vagal nerve-derived peptides.

Research Products

• [Journal Article] Bach1 deficiency protects pancreatic beta-cells from oxidative stress injury. (2013)
  • Author(s): Kondo K, Ishigaki Y, Gao J, Yamada T, Imai J, Sawada S, Muto A, Oka Y, Igarashi K, Katagiri H.
  • Journal Title: American Journal of Physiology Endocrinology & Metabolism Volume: 305(5)
  • DOI: 10.1152/ajpendo.00120.2013
  • Peer Reviewed
• [Journal Article] Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study (2013)
  • Author(s): Takagi M, Ishigaki Y, Uno K, Sawada S, Imai J, Kaneko K, Hasegawa Y, Yamada T, Tokita A, Iseki K, Kanno S, Nishio Y, Katagiri H and Mori E
  • Journal Title: BMC Neurology Volume: 13 Pages: 1-7
  • DOI: 10.1186/1471-2377-13-76
  • Peer Reviewed
• [Journal Article] Chronic mild stress alters circadian expressions ofmolecular clock genes in the liver (2013)
  • Author(s): Takahashi K, Yamada T, Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H.
  • Journal Title: American Journal of Physiology Endocrinology and Metabolism Volume: 304
  • DOI: 10.1152/ajpendo.00388.2012
  • Peer Reviewed
• [Journal Article] Importance of endothelial NF-#61547;B signaling in vascular remodeling and aortic aneurysm formation. (2013)
  • Author(s): Saito T, Hasegawa Y, Ishigaki Y, Yamada T, Gao J, Imai J, Uno K, Kaneko K, Ogihara T, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H.
  • Journal Title: Cardiovascular Research Volume: 97 Pages: 106-114
  • DOI: 10.1093/cvr/cvs298
  • Peer Reviewed
• [Journal Article] Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses (2013)
  • Author(s): Yoshida S, Aihara KI, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama KI, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T
  • Journal Title: Circulation. Volume: 128 Pages: 1728-1738
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 臓器間ネットワークによる膵β細胞の機能と量の調節 (2013)
  • Author(s): 今井 淳太、片桐 秀樹
  • Journal Title: Diabetes Frontier Volume: 24 Pages: 513-518
• [Journal Article] Chronic mild stress alters circadian expressions of molecular clock genes in the liver. (2013)
  • Author(s): Takahashi K, Yamada T (corresponding author), Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 304(3)
  • Peer Reviewed
• [Journal Article] Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. (2012)
  • Author(s): Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, Ishihara H, Oka Y, Katagiri H.
  • Journal Title: Cell Metabolism Volume: 16(6) Pages: 825-832
  • DOI: 10.1016/j.cmet.2012.11.006
  • Peer Reviewed
• [Journal Article] A case of slowly progressive type 1 diabetes with insulin independence maintained for 10 years with alpha-glucosidase inhibitor monotherapy (2012)
  • Author(s): Munakata Y, Yamada T, Takahashi K, Tsukita S, Sawada S, Imai J, Ishigaki Y, Oka Y, Katagiri H
  • Journal Title: Intern Med Volume: 51 Pages: 3391-3394
  • Peer Reviewed
• [Journal Article] Regulation of pancreatic beta-cells by inter-organ networks (2012)
  • Author(s): Imai J, Katagiri H
  • Journal Title: Nihon Rinsho Volume: 70 Suppl 3 Pages: 109-112
• [Journal Article] Blockade of the nuclear factor-kappaB pathway in the endothelium prevents insulin resistance and prolongs life spans (2012)
  • Author(s): Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T, Imai J, Uno K, Gao J, Kaneko K, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H
  • Journal Title: Circulation Volume: 125 Pages: 1122-1133
  • Peer Reviewed
• [Journal Article] Hepatic peroxisome proliferator-activatedreceptor-{gamma}-fat-specificprotein 27 pathway contributes to obesity-related hypertension via afferent vagal signals (2012)
  • Author(s): Uno K, Yamada T, Ishigaki Y, Imai J, Hasegawa Y, Gao J, Kaneko K, Matsusue K, Yamazaki T, Oka Y, Katagiri H
  • Journal Title: European Heart Journal Volume: (In Press) Pages: 1279-1289
  • DOI: 10.1093/eurheartj/ehr265
  • Peer Reviewed
• [Journal Article] TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance (2012)
  • Author(s): Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, Imai J et al,
  • Journal Title: Cell Metab Volume: 16 Pages: 825-32
  • Peer Reviewed
• [Journal Article] A case of slowly progressive type 1 diabetes with insulin independence maintained for 10 years with alpha-glucosidase inhibitor monotherapy. (2012)
  • Author(s): Munakata Y, Yamada T, Takahashi K, Tsukita S, Sawada S, Imai J et al.
  • Journal Title: Intern Med Volume: 51 Pages: 3391-3394
  • Peer Reviewed
• [Journal Article] NF-kappaB 経路と老化についての論文 (2012)
  • Author(s): Hasegawa Y, Saito T, Ogihara T, Imai J et al.
  • Journal Title: Circulation Volume: 125 Pages: 1122-1133
  • Peer Reviewed
• [Journal Article] CHOPの動脈硬化における役割についての論文 (2012)
  • Author(s): Gao J, Ishigaki Y, Yamada T, Imai J et al.
  • Journal Title: Circulation Volume: 124 Pages: 830-839
  • Peer Reviewed
• [Journal Article] Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic beta-cells : potential involvement of the PLC-IP3-dependent pathway (2011)
  • Author(s): Suzuki T, Imai J, Yamada T, IshigakiY, Kaneko K, Uno K, Hasegawa Y, Ishihara H, Oka Y, Katagiri H
  • Journal Title: Diabetes Volume: 60 Pages: 537-47
  • DOI: 10.2337/db10-0796
  • Peer Reviewed
• [Presentation] Regulation of pancreatic beta-cells by inter-organ networks (2013)
  • Author(s): Junta Imai
  • Organizer: Beta Cell Workshop 2013
  • Place of Presentation: 京都
  • Invited
• [Presentation] 神経シグナルを介した膵β細胞制御機構 (2013)
  • Author(s): 今井淳太
  • Organizer: 第56回日本糖尿病学会総会
  • Place of Presentation: 熊本(シンポジウム講演)
  • Year and Date: 2013-05-17
• [Presentation] Regulation of pancreatic beta-cells by inter-organ networks (2013)
  • Author(s): Imai J
  • Organizer: Beta Cell Workshop 2013
  • Place of Presentation: 京都(シンポジウム講演)
  • Year and Date: 2013-04-24
• [Presentation] 臓器間ネットワークによる膵β細胞制御機構, (2012)
  • Author(s): 今井 淳太
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Regulation of pancreatic beta-cells by Inter-organ Networks (2012)
  • Author(s): Junta Imai
  • Organizer: 第4回アジア糖尿病学会・第9回国際糖尿病連合西太平洋総会
  • Place of Presentation: 京都
  • Invited
• [Presentation] Regulation of pancreatic beta-cells by Inter-organ Networks (2012)
  • Author(s): Imai J
  • Organizer: 第4回アジア糖尿病学会・第9回国際糖尿病連合西太平洋総会
  • Place of Presentation: 京都(シンポジウム講演)
  • Year and Date: 2012-11-27
• [Presentation] 臓器間ネットワークによる膵β細胞制御機構 (2012)
  • Author(s): 今井淳太
  • Organizer: 第85回日本内分泌学会
  • Place of Presentation: 名古屋(シンポジウム講演)
  • Year and Date: 2012-04-19
• [Presentation] 臓器間連関と膵β細胞について (2011)
  • Author(s): Junta Imai
  • Organizer: 第54回日本糖尿病学会年次学術集会(招待講演)
  • Place of Presentation: 札幌
• [Presentation] 臓器間連関と膵β細胞について (2011)
  • Author(s): Junta Imai
  • Organizer: Strategic Japanese-Danish Cooperative Program(招待講演)
  • Place of Presentation: デンマーク、コペンハーゲン
• [Presentation] 臓器間連関と膵β細胞について (2011)
  • Author(s): Junta Imai
  • Organizer: Workshop Programming Beta Cell Development(招待講演)
  • Place of Presentation: デンマーク、ヘルシンガー
• [Presentation] Regulation of insulin secretion by Inter-organ Networks (2011)
  • Author(s): Imai J
  • Organizer: International Beta-cell work shop
  • Place of Presentation: デンマークヘルシンガー(シンポジウム講演)
  • Year and Date: 2011-10-25
• [Presentation] Regulation of pancreatic beta-cells by neuronal signal (2011)
  • Author(s): Imai J
  • Organizer: Strategic Japanese-Danish Cooperative Program on Molecular Diabetology
  • Place of Presentation: デンマークコペンハーゲン(シンポジウム講演)
  • Year and Date: 2011-10-21
• [Presentation] Regulation of Insulin Secretion by Inter-Organ Communications (2011)
  • Author(s): Imai J
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌(シンポジウム講演)
  • Year and Date: 2011-05-20
• [Book] 再生医療叢書5 (2012)
  • Author(s): 今井淳太
  • Publisher: 朝倉書店
• [Book] Helicobacter pylori感染とB型インスリン抵抗症 (2011)
  • Author(s): 今井淳太、山田哲也、岡芳知、片桐秀樹
  • Total Pages: 5
  • Publisher: 科学評論社
• [Book] ヘリコバクター・ピロリ除菌により治癒したB型インスリン抵抗症 (2011)
  • Author(s): 今井淳太、山田哲也、岡芳知、片桐秀樹
  • Total Pages: 3
  • Publisher: 中山書店
• [Patent(Industrial Property Rights)] 膵β細胞増殖促進剤、血中インスリン濃度上昇剤、血糖値低下剤・糖尿病治療・予防薬 (2013)
  • Inventor(s): 片桐 秀樹、岡 芳知、今井 淳太
  • Industrial Property Rights Holder: 片桐 秀樹、岡 芳知、今井 淳太
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2013-09-06
  • Acquisition Year: 2013
  • Overseas