New Conceptual Framework for Copy Number Variation-associated Diabetes

• Project/Area Number: 24659439
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Tohoku University
• Principal Investigator: KATAGIRI Hideki 東北大学, 医学(系)研究科(研究院), 教授 (00344664)
• Co-Investigator(Kenkyū-buntansha): MATSUZAKA Takashi 筑波大学, 医学医療系, 准教授 (70400679)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 2型糖尿病 / ゲノム / 疾患関連遺伝子

Research Abstract

Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24 and 22q13, which have significant associations with early-onset Japanese T2DM. Furthermore, copy number variation (CNV) analysis of the whole genome verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Thus, CNV within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM.

Research Products

• [Journal Article] Simultaneous copy number losses within multiple subtelomeric regions in early-onset type2 diabetes mellitus (2014)
  • Author(s): Kodama S, Yamada T, Imai J, Sawada S, Takahashi K, Tsukita S, Kaneko K, Uno K, Ishigaki Y, Oka Y, Katagiri H
  • Journal Title: PLoS One Volume: 9 Issue: 4 Pages: e88602-e88602
  • DOI: 10.1371/journal.pone.0088602
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bach1 deficiency protects pancreatic β-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: Am J Physiol Endocrinol Metab. Volume: 305(5) Issue: 5 Pages: E641-E648
  • 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 Neurol Volume: 13 Issue: 1 Pages: 76-76
  • DOI: 10.1186/1471-2377-13-76
  • Peer Reviewed
• [Journal Article] Clinical Experiences in the Treatment of Pancreatic Arteriovenous Malformation by Total Pancreatectomy With Islet Autotransplantation. (2013)
  • Author(s): Sakata N, Goto M, Motoi F, Hayashi H, Nakagawa K, Mizuma M, Yamaya H, Hasegawa Y, Yamaguchi S, Sawada S, Ottomo S, Okada T, Fukase K, Yoshida H, Ito T, Hirota M, Ishigaki Y, Sekiguchi S, Rikiyama T, Katayose Y, Fujimori K, Egawa S, Shimosegawa T, Katagiri H, Satomi S, Unno M
  • Journal Title: Transplantation Volume: 96(5) Issue: 5 Pages: e38-e40
  • DOI: 10.1097/tp.0b013e3182a01333
  • Peer Reviewed
• [Journal Article] Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization. (2013)
  • Author(s): Izumida Y, Yahagi N, Takeuchi Y, Nishi M, Shikama A, Takarada A, Masuda Y, Kubota M, Matsuzaka T, Nakagawa Y, Iizuka Y, Itaka K, Kataoka K, Shioda S, Niijima A, Yamada T, Katagiri H, Nagai R, Yamada N, Kadowaki T, Shimano H
  • Journal Title: Nat Commun. Volume: 4 Issue: 1 Pages: 2316-2316
  • DOI: 10.1038/ncomms3316
  • Peer Reviewed / Open Access
• [Journal Article] Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans (2012)
  • Author(s): Hasegawa Y, Fujita T, et al.
  • Journal Title: Circulation Volume: 125 Issue: 9 Pages: 1122
  • DOI: 10.1161/circulationaha.111.054346
  • Peer Reviewed
• [Journal Article] Atf6α-null mice are glucose intolerant due to pancreatic β-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance (2012)
  • Author(s): M.Usui, S.Yamaguchi, Y.Tanji, R.Tominaga, Y.Ishigaki, M.Fukumoto, H.Katagiri, K.Mori, Y.Oka, H.Ishihara
  • Journal Title: Metabol Volume: (in press) Issue: 8 Pages: 1118-28
  • DOI: 10.1016/j.metabol.2012.01.004
  • Peer Reviewed
• [Journal Article] Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-medeiated pathway (2012)
  • Author(s): Okada S, Yokoyama M, Toko H, Tateno K, Moriya J, Shimizu I, Nojima A, Ito T, Yoshida Y, Kobayashi Y, Katagiri H, Minamino T, Komuro I
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32(8) Issue: 8 Pages: 1902-9
  • DOI: 10.1161/atvbaha.112.248930
  • Peer Reviewed
• [Journal Article] A case of slowly progressive type 1 diabetes maintaining insulin independence for 10 years with α-glucosidase inhibitor monotherapy. (2012)
  • Author(s): Munakata Y, Yamada T, Takahashi K, Tsukita S, Takahashi K, Sawada S, Imai J, Ishigaki Y, Oka Y, Katagiri H
  • Journal Title: Internal Medicine Volume: 51(24) Pages: 3391-3394
  • Peer Reviewed
• [Journal Article] Importance of endothelial NF-κB signaling in vascular remodeling and aortic aneurysm formation (2012)
  • 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(1) Issue: 1 Pages: 106-114
  • DOI: 10.1093/cvr/cvs298
  • 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 Metab Volume: 16(6) Pages: 825-832
  • Peer Reviewed
• [Journal Article] Chronic mild stress alters circadian expressions of molecular clock genes in the liver (2012)
  • 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: Am J Physiol Endocrinol Metab Volume: 304 Issue: 3 Pages: E301-E309
  • DOI: 10.1152/ajpendo.00388.2012
  • Peer Reviewed
• [Presentation] 臓器間ネットワークからみた肥満・2型糖尿病（シンポジウム6：臓器からみた糖尿病の病態と治療） (2014)
  • Author(s): 山田哲也, 片桐秀樹
  • Organizer: 第48回 糖尿病学の進歩
  • Place of Presentation: 札幌
  • Invited
• [Presentation] 全ゲノムCNV解析による若年発症2型糖尿病患者における複数領域の高頻度ゲノム欠失 (2013)
  • Author(s): 児玉慎二郎、山田哲也、江見充、工藤宏仁、石井美穂、佐藤秀則、澤田正二郎、今井淳太、石垣泰、岡芳知、片桐秀樹
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 臓器間神経ネットワークによる個体レベルでのエネルギー代謝制御機構 (2013)
  • Author(s): 片桐秀樹
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] 肝からの臓器間ネットワークによるエネルギー代謝制御 (2013)
  • Author(s): 山田哲也, 突田壮平, 岡芳知, 片桐秀樹
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] 神経シグナルを介した膵β細胞量制御機構 (2013)
  • Author(s): 今井淳太, 片桐秀樹
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Neuronal information highways for systemic regulation of glucose and energy metabolism (2013)
  • Author(s): Katagiri Hideki
  • Organizer: The 36th Naito Conference (第36回内藤コンファレンス)
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] メタボリックインフォメーションハイウェイ (2013)
  • Author(s): 片桐秀樹
  • Organizer: 第11回日本糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Neuronal Information Highways for Systemic Regulation of Glucose and Energy Metabolism (2013)
  • Author(s): Hideki Katagiri
  • Organizer: International Symposium on Development of Medical Technologies for Treating Intractable Cancers and Cardiovascular Diseases
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] 臓器間ネットワークとメタボリックシンドローム (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 糖代謝と自律神経：神経ネットワークの解明 (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 褐色脂肪組織における熱産生調節につながる組織間ネットワーク (2012)
  • Author(s): 突田壮平、山田哲也、宇野健司、高橋圭、浅井洋一郎、白井勇太、宗像佑一郎、金子慶三、澤田正二郎、長谷川豊、今井淳太、石垣泰、岡芳知、片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 継続した避難所巡回診療により見えてきた災害時の糖尿病医療の問題点とその対策 (2012)
  • Author(s): 児玉慎二郎、石垣泰、今井淳太、山田哲也、岡芳知、片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] mTOR抑制因子であるDEPTORが糖エネルギー代謝に与える影響の解明 (2012)
  • Author(s): 千葉弓子、宇野健司、片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 動脈硬化を操る代謝シグナルネットワークの解明から治療へ The atherosclerosis puzzle:Bringing up new Matabolic pieces (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 多臓器連環による循環・代謝のダイナミズム (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第16回日本心血管内分泌代謝学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 神経系を介した臓器間相互作用による体重調整 (2012)
  • Author(s): 山田哲也、岡芳知、片桐秀樹
  • Organizer: 第16回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Hepatic Glucokinase Negatively Regulates BAT Thermogenesis via a Neural Pathway (2012)
  • Author(s): Sohei Tsukita, Tetsuya Yamada, Kenji Uno, Yoshitomo Oka, Hideki Katagiri
  • Organizer: 72nd American Diabetes Association
  • Place of Presentation: Philadelphia,USA
  • Invited
• [Presentation] Bach1 deficiency protects pancreatic beta cells from oxidative stress injury (2012)
  • Author(s): Keiichi Kondo, Y. Ishigaki, J. Gao, T. Yamada, J. Imai, S. Sawada, A. Muto, Y. Oka, K. Igarashi, H. Katagiri
  • Organizer: 48th European Association for the Study of Diabetes Annual Meeting
  • Place of Presentation: Berlin,Germany
  • Invited
• [Presentation] 糖尿病合併高度肥満に対する肥満手術１年後の持続血糖モニター（continuous glucose monitoring; CGM）で捉えた血糖プロフィール
  • Author(s): 澤田正二郎, 石垣泰, 今井淳太, 山田哲也, 内藤剛, 柴田近, 佐々木巌, 岡芳知, 片桐秀樹
  • Organizer: 第31回日本肥満症治療学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 1型糖尿病と2型糖尿病の頚動脈血管壁弾性特性の比較検討
  • Author(s): 澤田正二郎, 石垣泰, 長谷川英之, 鴇田藍, 本蔵理恵子, 金子礼, 今井淳太, 山田哲也, 宮地幸哉, 金井浩, 岡芳知, 片桐秀樹
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Metabolic Information Highways～個体レベルでの代謝調節と寿命制御～
  • Author(s): 片桐秀樹
  • Organizer: 第18回糖尿病医学研究科
  • Place of Presentation: 東京
  • Invited
• [Presentation] 肝GKによるBAT熱産生低下が個体のエネルギー代謝に及ぼす効果は飼育温度に影響される
  • Author(s): 突田壮平, 山田哲也, 宇野健司, 高橋圭, 金子慶三, 白井勇太, 宗像佑一郎, 児玉慎二郎, 浅井洋一郎, 椙澤貴志, 千葉弓子, 澤田正二郎, 今井淳太, 石垣泰, 片桐秀樹
  • Organizer: 第34回日本肥満学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Metabolic Information Hiways～個体レベルでの糖代謝・エネルギー代謝調節システム～
  • Author(s): 片桐秀樹
  • Organizer: 糖尿病とCKDシンポジウム
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 臓器間ネットワークによる膵β細胞制御機構
  • Author(s): 今井 淳太、片桐 秀樹
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 神経系を介した臓器間相互作用による体重調節機構
  • Author(s): 山田哲也、片桐秀樹、岡 芳知
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 非侵襲的陽圧換気療法の使用により著明な体重減少を呈した肥満低換気症候群の一例
  • Author(s): 浅井 洋一郎、宇野 健司、田中 満実子、宗像 佑一郎、高橋 圭、今井 淳太、山田 哲也、石垣 泰、岡 芳知、片桐 秀樹
  • Organizer: 第30回日本肥満症治療学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 個体レベルでの代謝調節と循環～血圧から寿命の制御まで～
  • Author(s): 片桐 秀樹
  • Organizer: 第1回日本肺循環学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Metabolic Information Highway～個体レベルでの代謝制御機構～
  • Author(s): 片桐 秀樹
  • Organizer: 神経組織の成長・再生・移植研究会第27回学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Regulation of pancreatic beta-cells by Inter-organ Networks
  • Author(s): Junta Imai, Hideki Katagiri
  • 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