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Investigation of molecular mechanisms for the regulation of insulin secretion by KCNQ1

Research Project

Project/Area Number 22591021
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

MAEDA Shiro  独立行政法人理化学研究所, 内分泌・代謝疾患研究チーム, チームリーダー (50314159)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords2型糖尿病 / 膵β細胞 / インスリン分泌 / GLP-1分泌 / 遺伝子 / 遺伝因子
Research Abstract

We identified that inhibition of KCNQ1 enhanced glucose-induced insulin secretion in rat isolated pancreatic beta cells, and bethanecol-induced glucagon like peptide-1 secretion in NCI-H716 cells. In addition, we have found that KCNQ1 risk variants for type 2 diabetes were negatively correlated with beta cell function (HOMA-beta) in non-diabetic individuals, and an accumulation of type 2 diabetes risk variants, including KCNQ1 variants, was associated with requirement of insulin injection in patients with type 2 diabetes.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (39 results)

All 2013 2012 2011 2010

All Journal Article (25 results) (of which Peer Reviewed: 23 results) Presentation (14 results)

  • [Journal Article] Replication study for the association of a single nucleotide polymorphism, rs3746876, within KCNJ15, with susceptibility to type 2 diabetes in a Japanese population2013

    • Author(s)
      Fukuda H, Imamura M, Tanaka Y, Iwata M, Hirose H, Kaku K, Maegawa H, Watada H, Tobe K, Kashiwagi A, Kawamori R, Maeda S
    • Journal Title

      J Hum Genet 2013

      Volume: (in press)

    • NAID

      10031190046

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX42013

    • Author(s)
      Ma RCW, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, Thomas GN, Go MJ, Hara K, Sim X, Ho JSK, Wang C, Li H, Lu L, Wang Y, Li JW, Wang Y, Lam VKL, Wang J, Yu W, Kim Y, Ng DP, Fujita H, Panoutsopoulou K, Day-Williams A, Lee HM, Ng ACW, Fang Y, Kong APS, Jiang F, Ma X, Hou X, Tang S, Lu J, Yamauchi T, Tsui SKW, Woo JLF, Leung PC, Zhang X, Tang NLS, Sy HY, Liu J, Wong TY, Lee JY, Maeda S, Xu G, Cherny SS, Chan TF, Ng MCY, Xiang K, Morris AP, DIAGRAM Consortium, Keildson S, MuTHER Consortium, Hu R, Ji L, Lin X, Cho YS, Kadowaki T, Tai ES, Zeggini E, McCarthy MI, Hon KL, Baum L, Tomlinson B, So WY, Bao Y, Chan JCN, Jia W
    • Journal Title

      Diabetologia

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India2013

    • Author(s)
      Saxena R, Saleheen D, Been LF, Garavito ML, Bjonnes A, Young R, Ho WK, Rasheed A, Frossard P, Sim X, Hassanali N, Radha V, Chidambaram M, Liju S, Rees SD, Ng DPK, Wong T-Y, Yamauchi T, Hara K, Tanaka Y, Hirose H, McCarthy MI, Morris AP, DIAGRAM, MuTHER, AGEN, Basit A, Barnett AH, Katulanda P, Matthews D, Mohan V, Wander GS, Singh JR, Mehra NK, Ralhan S, Kamboh MI, Mulvihill JJ, Maegawa H, Tobe K, Maeda S, Cho YS, Tai ES, Kelly MA, Chambers JC, Kooner JS, Kadowaki T, Deloukas P, Danesh J, Sanghera DK
    • Journal Title

      Diabetes

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A replication study for the association of rs391300 in SRR and rs17584499 in PTPRD with susceptibility to type 2 diabetes in the Japanese2013

    • Author(s)
      Imamura M, Iwata M, Maegawa H, Watada H, Hirose H, Tanaka Y, Tobe K, Kaku K, Kashiwagi A, Kadowaki T, Kawamori R, Maeda S
    • Journal Title

      J Diabetes Invest

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population2012

    • Author(s)
      Fukuda H, Imamura M, Tanaka Y, Iwata M, Hirose H, Kaku K, Maegawa H, Watada H, Tobe K, Kashiwagi A, Kawamori R, Maeda S
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] KCNQ1 SNPs and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes2012

    • Author(s)
      Lim XL, Nurbaya S, Tai ES, Maeda S. Nakamura Y, Ng DPK
    • Journal Title

      Diabetologia

      Volume: 55 Pages: 2402-2406

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals2012

    • Author(s)
      Iwata M, Maeda S, Kamura Y, Takano A, Kato H, Murakami S, Higuchi K, Takahashi A, Fujita H, Hara K, Kadowaki T, Tobe K
    • Journal Title

      Diabetes Care

      Volume: 35 Pages: 1763-1770

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations2012

    • Author(s)
      Imamura M, Maeda S, Yamauchi T, Hara K, Yasuda K, Morizono T, Takahashi A, Horikosi M, Nakamura M, Fujita H, Tsunoda T, Kubo M, Watada H, Maegawa H, Okada-Iwabu M, Iwabu M, Shojima N, Ohshige T, Omori S, Iwata M, Hirose H, Kaku K, Ito C, Tanaka Y, Tobe K, Kashiwagi A, Kawamori R, Kasuga M, Kamatani N, DIAGRAM consortium, Nakamura Y, Kadowaki T
    • Journal Title

      Hum Mol Genet

      Volume: 21 Pages: 3042-3049

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression-based genome-wide association study links CD44 in adipose tissue with type 2 diabetes2012

    • Author(s)
      Kodama M, Horikoshi M, Toda K, Yamada S, Hara K, Irie J, Sirota M, Morgan AA, Chen R, Ohtsu H, Maeda S, Kadowaki T, Butte AJ
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Pages: 7049-7054

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Meta-analysis of genome-wide association studies identifies 8 new loci for type 2 diabetes in East Asians2012

    • Author(s)
      Cho YS, Chen C-H, Hu C, Long J, Ong RTH, Sim X, Takeuchi F, Wu Y, Go MJ, Yamauchi T, Chang Y-C, Kwak SH, Ma RCW, Yamamoto K, Adair LS, Aung T, Cai Q, Chang L-C, Chen Y-T, Gao Y, Hu FB, Kim H-L, Kim S, Kim YJ, Lee JJ-M, Lee NR, Li Y, Liu JJ, Lu W, Nakamura J, Nakashima E, Ng DPK, Tay WT, Tsai F-J, Wong TY, Yokota M, Zheng W, Zhang R, Wang C, So WY, Ohnaka K, Ikegami H, Hara K, Cho YM, Cho NH, Chang TJ, Bao Y, Hedman AK, Morris AP, McCarthy MI, DIAGRAM consortium, MuTHER consortium, Takayanagi R, Park KS, Jia W, Chuang L-M, Chan JCN, Maeda S, Kadowaki T, Lee J-Y, Wu J-Y, Teo YY, Tai ES, Shu XO, Mohlke KL, Kato N, Han B-G, Seielstad M
    • Journal Title

      Nature Genetics

      Volume: 44 Pages: 67-72

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals2012

    • Author(s)
      Iwata M, Hara K, Kadowaki T
    • Journal Title

      Diabetes Care

      Volume: 35 Issue: 8 Pages: 1763-1770

    • DOI

      10.2337/dc11-2006

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations.2012

    • Author(s)
      Imamura M, Maeda S, Yamauchi T, Hara K, Yasuda K,..., Okada-Iwabu M, Iwabu M, Shojima N,..., Nakamura Y, Kadowaki T
    • Journal Title

      Human Molecular Genetics

      Volume: 21 Issue: 13 Pages: 3042-3049

    • DOI

      10.1093/hmg/dds113

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population.2012

    • Author(s)
      Hisashi Fukuda
    • Journal Title

      PLoS One

      Volume: 7 Issue: 9 Pages: e46263-e46263

    • DOI

      10.1371/journal.pone.0046263

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of New Loci Identified in European Genome-wide Association Studies with Susceptibility to Type 2 Diabetes in the Japanese2011

    • Author(s)
      Ohshige T, Iwata M, Omori S, Tanaka Y, Hirose H, Kaku K, Maegawa H, Watada H, Kashiwagi A, Kawamori R, Tobe T, Kadowaki T, Nakamura Y, Maeda S
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic variants at CDC123/CAMK1D and SPRY2 are associated with susceptibility to type 2 diabetes in the Japanese population2011

    • Author(s)
      Imamura M, Iwata M, Maegawa H, Watada H, Hirose H, Tanaka Y, Tobe K, Kaku K, Kashiwagi A, Kawamori R, Nakamura Y, Maeda S
    • Journal Title

      Diabetologia

      Volume: 54 Pages: 3071-3077

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetics of type 2 diabetes; GWAS era and the future perspectives2011

    • Author(s)
      Imamura M, Maeda S
    • Journal Title

      Endocrine J

      Volume: 58 Pages: 723-739

    • NAID

      10029862564

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals2011

    • Author(s)
      Grarup N, Overvad M, SparsφT, Witte DR, Pisinger C, Jφrgensen T, Yamauchi T, Hara K, Maeda S, Kadowaki T, Hansen T
    • Journal Title

      Diabetologia

      Volume: 54 Pages: 789-794

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetics of type 2 diabetes: the GWAS era and future perspectives [Review]2011

    • Author(s)
      Imamura M, Maeda S
    • Journal Title

      Endocrine Journal

      Volume: 58 Issue: 9 Pages: 723-739

    • DOI

      10.1507/endocrj.EJ11-0113

    • NAID

      130004443740

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic variants at CDC123/CAMK1D and SPEY2 are associated with susceptibility to type 2 diabetes in the Japanese population2011

    • Author(s)
      Imamura, et al
    • Journal Title

      Diabetologia

      Volume: 54 Issue: 12 Pages: 3071-3077

    • DOI

      10.1007/s00125-011-2293-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of New Loci Identified in European Genome-wide Association Studies witb Susceptibility to Type 2 Diabetes in the Japanese2011

    • Author(s)
      Ohshige T, et al
    • Journal Title

      PLoS One

      Volume: 6 Issue: 10 Pages: e26911-e26911

    • DOI

      10.1371/journal.pone.0026911

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A/B2010

    • Author(s)
      Yamauchi T, Hara K, Maeda S, Yasuda K, Takahashi A, Horikoshi M, Nakamura M, Fujita H, Grarup N, Cauchi S, Ng DPK, Ma RCW, Tsunoda T, Kubo M, Watada H, Maegawa H, Okada-Iwabu M, Iwabu M, Shojima N, Shin HD, Andersen G, Witte DR, Jφrgensen T, Lauritzen T, Sandbaek A, Hansen T, Ohshige T, Omori S, Saito I, Kaku K, Hirose H, So WY, Beury D, Chan JCN, Park KS, Tai ES, Ito C, Tanaka Y, Kashiwagi A, Kawamori R, Kasuga M, Frogue P, Pedersen O, Kamatani N, Nakamura Y & Kadowaki T
    • Journal Title

      Nat Genet

      Volume: 42 Pages: 864-868

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A single nucleotide polymorphism in KCNQ1 is associated with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes2010

    • Author(s)
      Ohshige T, Tanaka Y, Araki S, Babazono T, Toyoda M, Umezono T, Watada H, Suzuki D, Iwamoto Y, Kawamori R, Nakamura Y, Maeda S
    • Journal Title

      Diabetes Care

      Volume: 33 Pages: 842-846

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 代謝性疾患の遺伝子学2010

    • Author(s)
      前田士郎、鎌谷直之
    • Journal Title

      最新医学

      Volume: 65 Pages: 2008-2019

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 2型糖尿病の遺伝とは2010

    • Author(s)
      前田士郎
    • Journal Title

      最新医学

      Volume: 65 Pages: 2111-2121

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Overexpression of Acetyl-Coenzyme A Carboxylase Beta Increases Pro-Inflammatory Cytokines in Cultured Human Renal Proximal Tubular Epithelial Cells.2010

    • Author(s)
      Kobayashi M, et al.
    • Journal Title

      Clin Exp Nephrol

      Volume: 14 Pages: 315-324

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Genetic variations in DUSP9 locus and CMIP locus are associated with type 2 diabetes in a Japanese population2012

    • Author(s)
      Imamura M, Fukuda H, Iwata M, Maegawa H, Watada H, Hirose H, Tanaka Y, Tobe K, Kaku K, Kashiwagi A, Kawamori R, Maeda S
    • Organizer
      47th Annual Meeting of the European Association for the Study of Diabetes
    • Place of Presentation
      Berlin, Germeny
    • Year and Date
      2012-10-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Imputationに基づくゲノムワイド関連解析による2型糖尿病疾患感受性遺伝子領域の同定2012

    • Author(s)
      今村美菜子, 前田士郎, 山内敏正, 原一雄, 安田一基, 綿田裕孝, 前川聡, 岩田実, 広瀬寛, 加来浩平, 伊藤千賀子, 田中逸, 戸辺一之, 柏木厚典, 河盛隆造, 春日雅人, 中村祐輔, 門脇孝
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2012-05-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Genetic variations in DUSP9 locus and CMIP locus are associated with type 2 diabetes in a Japanese population2012

    • Author(s)
      Minako Imamura
    • Organizer
      48th European Association for the study of diabetes Annual Meeting
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] Rs10906115 in CDC123/CAMK1D locus and rs1359790 near SPRY2 are associated with susceptibility to type 2 diabetes in a Japanese population2011

    • Author(s)
      Imamura M, Iwata M, Maegawa H, Watada H, Hirose H, Tanaka Y, Tobe K, Kaku K, Kashiwagi A, Kawamori R, Nakamura Y, Maeda S
    • Organizer
      46th Annual Meeting of the European Association for the Study of Diabetes
    • Place of Presentation
      Lisbon, Portugal
    • Year and Date
      2011-09-15
    • Related Report
      2012 Final Research Report
  • [Presentation] KCNQ1 and genetic susceptibility to diabetic nephropathy in type 2 diabetes : replication in the Singaporean Chinese population2011

    • Author(s)
      Ng, et al
    • Organizer
      The European Association for the Study of Diabetes 47^<th> Annual meeting
    • Place of Presentation
      Lisbon
    • Year and Date
      2011-09-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Rs10906115 in CDC123/CAMK10 locus and rs1359790 near SPRY2 are associated with susceptibility to type 2 diabetes in a Japanese population2011

    • Author(s)
      Imamura, et al
    • Organizer
      American Diabetes Association 71^<st> Scientific Sessions
    • Place of Presentation
      San Diego
    • Year and Date
      2011-06-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] 2型糖尿病感受性候補領域23領域の日本人集団における検証2011

    • Author(s)
      大重 聡彦, 大森 慎太郎, 田中 逸, 柏木 厚典, 加来 浩平, 広瀬 寛, 河盛 隆造, 中村 祐輔, 前田 士郎
    • Organizer
      第53回日本糖尿病学会
    • Place of Presentation
      岡山
    • Year and Date
      2011-05-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 2型糖尿病感受性候補領域33領域の日本人集団における検証2011

    • Author(s)
      今村美菜子、田中逸、前川 聡、綿田 裕孝、柏木厚典、加来浩平、広瀬寛、河盛 隆造、中村祐輔、前田士郎
    • Organizer
      第54回日本糖尿病学会
    • Place of Presentation
      札幌
    • Year and Date
      2011-05-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 全ゲノム解析と発現解析による2型糖尿病関連遺伝子同定の試み2011

    • Author(s)
      原 一雄、藤田 逸人、庄嶋 伸浩、掘越 桃子、岡崎 由希子、前田 士郎、山内 敏正、植木 浩二郎、門脇 孝
    • Organizer
      第54回日本糖尿病学会
    • Place of Presentation
      札幌
    • Year and Date
      2011-05-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Effects of KCNQ1 on glucose-induced insulin secretion in rat pancreatic beta cells or on glucagon-like peptide-1 secretion in cultured NCI-H716 cells2010

    • Author(s)
      Maeda S, Tsukada S
    • Organizer
      46th Annual Meeting of the European Association for the Study of Diabetes
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2010-09-22
    • Related Report
      2012 Final Research Report
  • [Presentation] Effects of KCNQ1 on Glucose-Induced Insulin Secretion in rat pancreatic ss cells or on Glucagon-Like Peptide-1 secretion in cultured NCI-H716 cells2010

    • Author(s)
      Maeda S, et al.
    • Organizer
      46^<th> Annual meeting, The European Association for the Study of Diabetes
    • Place of Presentation
      ストックホルム,スウェーデン
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Replication Study for the Association of 23 Susceptibility Loci for Type 22010

    • Author(s)
      Oshige T, Omori S, Tanaka Y, Kashiwagi A, Kaku K, Hirose H, Kawamori R, Nakamura Y, Maeda S
    • Organizer
      Diabetes in the Japanese American Diabetes Association 70th Scientific Sessions
    • Place of Presentation
      Orland U.S.A.
    • Year and Date
      2010-06-26
    • Related Report
      2012 Final Research Report
  • [Presentation] 2型糖尿病患者のゲノム解析2010

    • Author(s)
      前田 士郎
    • Organizer
      第53回日本糖尿病学会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-29
    • Related Report
      2012 Final Research Report
  • [Presentation] single nucleotide polymorphism in KCNQ1 is associated with diabetic nephropathy in Japanese subjects with type 2 diabetes"2010

    • Author(s)
      Maeda S., Oshige T., Araki S., Tomoya U., Toyoda M.,Kawai K., Imanishi M., Uzu T., Babazono T., Watada H., Suzuki D., Tanaka Y., Kashiwagi A., Iwamoto Y.,Kawamori R., and Nakamura Y
    • Organizer
      International Society of Nephrology (ISN-nexus), (International Society of Nephrology)
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-04-16
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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