Realization of Preemptive Medicine by elucidating the onset mechanism of diabetes attributed to mismatch between Constitution and Environment

• Project/Area Number: 16K01834
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: TAKA HIKARI 順天堂大学, 医学(系)研究科(研究院), 助教 (60338374)
• Co-Investigator(Kenkyū-buntansha): 加賀 直子 順天堂大学, 医学(系)研究科(研究院), 助教 (80338342)
• Research Collaborator: NEMOTO takahiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 生活習慣病 / 2型糖尿病 / DOHaD仮説 / キャピラリー電気泳動質量分析 / 質量分析 / 低体重児

Outline of Final Research Achievements

According to Developmental Origins of Health and Disease (DOHaD) theory, low birth weight is a risk factor for various Non-Communicable chronic diseases (NCDs), such as hypertension, heart disease, type 2 diabetes and mental illness. However, the mechanisms that increase the risk of NCDs in low birth weight infants have not been elucidated yet. In order to identify the risk factors for NCDs caused by mismatch between constitution and environment, offspring of rats were divided into two groups by their birth weight and then fed a high fat diet to both groups. We analyzed serum metabolites of each group with a capillary electrophoresis-mass spectrometry (CE-MS), followed by statistical analysis. As a result, we found several candidates for the risk factor of type2 diabetes in low birth weight group.

Academic Significance and Societal Importance of the Research Achievements

生活習慣病は今や健康長寿の最大の阻害要因となるだけでなく、国民医療費にも大きな影響を与えている。特に糖尿病は重症化すると細小血管症（糖尿病性網膜症、糖尿病性腎症、糖尿病性神経障害）、大血管障害（脳卒中、心筋梗塞、抹消動脈性疾患）など様々な合併症を誘発し、生活機能低下がおこり介護が必要となる。医療費だけでなく、介護にも多大な費用が必要となる。
この研究により糖尿病と相関性のある有益な早期バイオマーカーが確定できれば、発症リスクを持った子供たちが成人になる前に疾病の予防、治療が可能となり、国の医療費、介護費負担が軽減され、疾病リスクを負って産まれても健康で長生きできる健康長寿が結果とされる。

Research Products

• [Journal Article] Choline-related metabolites influenced by feeding patterns in preterm and term infants (2018)
  • Author(s): Shoji Hiromichi、Taka Hikari、Kaga Naoko、Ikeda Naho、Hisata Ken、Miura Yoshiki、Shimizu Toshiaki
  • Journal Title: The Journal of Maternal-Fetal & Neonatal Medicine Volume: ー Issue: 2 Pages: 1-6
  • DOI: 10.1080/14767058.2018.1488165
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine. (2018)
  • Author(s): Tabe Y, Saitoh K, Yang H, Sekihara K, Yamatani K, Ruvolo V, Taka H, Kaga N, Kikkawa M, Arai H, Miida T, Andreeff M, Spagnuolo PA, Konopleva M.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 16837-16837
  • DOI: 10.1038/s41598-018-35198-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. (2018)
  • Author(s): Fujimaki M, Saiki S, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N.
  • Journal Title: Neurology. Volume: 90 Issue: 5 Pages: 1-8
  • DOI: 10.1212/wnl.0000000000004888
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease. (2017)
  • Author(s): Shigiyama F, Kumashiro N, Furukawa Y, Funayama T, Takeno K, Wakui N, Ikehara T, Nagai H, Taka H, Fujimura T, Uchino H, Tamura Y, Watada H, Nemoto T, Shiraga N, Sumino Y, Hirose T.
  • Journal Title: Hepatol Commun. Volume: 1 Issue: 7 Pages: 634-647
  • DOI: 10.1002/hep4.1077
  • Peer Reviewed / Open Access
• [Journal Article] A pilot study of the effect of human breast milk on urinary metabolome analysis in infants. (2017)
  • Author(s): Shoji H, Taka H, Kaga N, Ikeda N, Kitamura T, Miura Y, Shimizu T.
  • Journal Title: J Pediatr Endocrinol Metab. Volume: 30 Issue: 9 Pages: 939-946
  • DOI: 10.1515/jpem-2017-0179
  • Peer Reviewed / Open Access
• [Journal Article] Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-1. (2017)
  • Author(s): Sekihara K, Saitoh K, Han L, Ciurea S, Yamamoto S, Kikkawa M, Kazuno S, Taka H, Kaga N, Arai H, Miida T, Andreeff M, Konopleva M, Tabe Y.
  • Journal Title: Oncotarget Volume: in press Issue: 21 Pages: 34552-34564
  • DOI: 10.18632/oncotarget.16602
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Combination of glycopyrronium and indacaterol inhibits carbachol-induced ERK5 signal in fibrotic processes. (2017)
  • Author(s): Namba Y, Togo S, Tulafu M, Kadoya K, Nagahama KY, Taka H, Kaga N, Orimo A, Liu X, Takahashi K.
  • Journal Title: Respir Res. Volume: 18 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s12931-017-0529-6
  • Peer Reviewed / Open Access
• [Journal Article] Amino group carrier protein-mediated secondary metabolite biosynthesis in Streptomyces. (2016)
  • Author(s): Hasebe, F., Matsuda, K., Shiraishi, T., Futamura, Y., Nakano, T., Tomita, T., Ishigami, K., Taka, H., Mineki, R., Fujimura, T., Osada, H., Kuzuyama, T., Nishiyama, M.
  • Journal Title: Nature Chemical Biology Volume: 12 Issue: 11 Pages: 967-972
  • DOI: 10.1038/nchembio.2181
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids. (2016)
  • Author(s): Morales J, Hashimoto M, Williams TA, Hirawake-Mogi H, Makiuchi T, Tsubouchi A, Kaga N, Taka H, Fujimura T, Koike M, Mita T, Bringaud F, Concepcion JL, Hashimoto T, Embley TM, Nara T.
  • Journal Title: Proc R Soc B Volume: 283 Issue: 1830 Pages: 20160520-20160520
  • DOI: 10.1098/rspb.2016.0520
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relation between insulin sensitivity and metabolic abnormalities in Japanese men with BMI of 23-25 kg/m2. (2016)
  • Author(s): Takeno K, Tamura Y, Kawaguchi M, Kakehi S, Watanabe T, Funayama T, Furukawa Y, Kaga H, Yamamoto R, Kim M, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Taka H, Fujimura T, Sawada SS, Giacca A, Kanazawa A, Fujitani Y, Kawamori R, Watada H.
  • Journal Title: J Clin Endocrinol Metab. Volume: 101 Issue: 10 Pages: 3676-3684
  • DOI: 10.1210/jc.2016-1650
  • Peer Reviewed / Open Access
• [Presentation] 低出生体重仔への高脂肪食負荷による非感染性慢性疾患（NCDｓ）発症リスクへの影響 (2018)
  • Author(s): 高ひかり、加賀直子、上野隆、三浦芳樹、根本崇宏
  • Organizer: 第91回日本生化学会大会
• [Presentation] 低出生体重仔における非感染性慢性疾患発症機序の解明 (2016)
  • Author(s): 加賀 直子、高 ひかり、上野隆、根本崇宏
  • Organizer: 第10回メタボロームシンポジウム
  • Place of Presentation: 山形県鶴岡市
  • Year and Date: 2016-10-19