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Analysis of islet amyloid in Japanese type 2 diabetic patients and exploration of new treatment for diabetes

Research Project

Project/Area Number 24659158
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionHirosaki University

Principal Investigator

YAGIHASHI Soroku  弘前大学, 医学(系)研究科(研究院), 教授 (40111231)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖尿病 / β細胞 / アミロイド / マクロファージ / 炎症 / 膵ランゲルハンス島 / 病理 / 形態計測 / 2型糖尿病 / ランゲルハンス島 / アポトーシス / サイトカイン
Research Abstract

We investigated islet amyloid deposition in Japanese type 2 diabetic patients. Different from high prevalence in Western diabetic patients, amyloid deposition was found in 28% of Japanese patients, occupying 18% area of the islet. The amyloid-rich diabetic group was associated with high BMI, indicating the implication of insulin resistance in the evolution of amyloid deposition. The beta cell volume density in amyloid-rich diabetic group was significantly smaller than that in amyloid-free diabetic group, suggesting that amyloid promotes the beta cell decline. The amyloid deposition was also accompanied by robust infiltration of activated macrophages. Thus, the intervention of the amyloid deposition and consequent inflammatory sequelae could be a novel target for the treatment of type 2 diabetes.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (47 results)

All 2014 2013 2012

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (25 results) (of which Invited: 5 results) Book (5 results)

  • [Journal Article] Involvement of oxidative stress-induced DNA damage, endoplasmic reticulum stress, and autophagy deficits in the decline ofβ-cell mass in Japanese type 2 diabetic patients2014

    • Author(s)
      Mizukami H, Takahashi K, Inaba W, Tsuboi K, Osonoi S, Yoshida T, Yagihashi S
    • Journal Title

      Diabetes Care 2014 Apr 4

      Volume: [Epub ahead of print](PMID:24705612)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Age-associated changes of islet endocrine cells and the effects of body mass index in Japanese2014

    • Author(s)
      Mizukami H, Takahashi K, Inaba W, Osonoi S, Kamata K, Tsuboi K, Yagihashi S
    • Journal Title

      J Diabetes Invest

      Volume: 5 Issue: 1 Pages: 38-47

    • DOI

      10.1111/jdi.12118

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance.2014

    • Author(s)
      Nagao M, Asai A, Inaba W, Kawahara M, Shuto Y, Kobayashi S, Sanoyama D, Sugihara H, Yagihashi S, Oikawa S
    • Journal Title

      PLoS One

      Volume: 9 Issue: 1 Pages: e84725-e84725

    • DOI

      10.1371/journal.pone.0084725

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of oxidative stress-induced DNA damage, endoplasmic reticulum stress, and autophagy deficits in the decline of β-cell mass in Japanese type 2 diabetic patients2014

    • Author(s)
      Mizukami H, Takahashi K, Inaba W, Tsuboi K, Osonoi S, Yoshida T, Yagihashi S.
    • Journal Title

      Diabetes Care

      Volume: 37

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance2014

    • Author(s)
      Nagao M, Asai A, Inaba W, Kawahara M, Shuto Y, Kobayashi S, Sanoyama D, Sugihara H, Yagihashi S, Oikawa S
    • Journal Title

      PLoS One

      Volume: 9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exendin-4 improves β-cell function in autophagy-deficient β-cells.2013

    • Author(s)
      Abe H, Uchida T, Hara A, Mizukami H, Komiya K, Koike M, Shigihara N, Toyofuku
    • Journal Title

      Endocrinology

      Volume: 154 Issue: 12 Pages: 4512-24

    • DOI

      10.1210/en.2013-1578

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The effects of dipeptidyl-peptidase-IV inhibitor, vildagliptin, on the exocrine pancreas in spontaneously diabetic Goto-Kakizaki rats2013

    • Author(s)
      Mizukami H, Inaba W, Takahashi K, Kamata K, Tsuboi K, Yagihashi S
    • Journal Title

      Pancreas

      Volume: 42 Issue: 5 Pages: 786-794

    • DOI

      10.1097/mpa.0b013e318287c9b5

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The impact of low-dose insulin on peripheral nerve insulin receptor signaling in streptozotocin-induced diabetic rats2013

    • Author(s)
      Sugimoto K, Baba M, Suzuki S, Yagihashi S
    • Journal Title

      PLoS One

      Volume: 8 Issue: 8 Pages: e74247-e74247

    • DOI

      10.1371/journal.pone.0074247

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Exendin-4 improves β-cell function in autophagy-deficient β-cell2013

    • Author(s)
      Abe H, Uchida T, Hara A, Mizukami H, Komiya K, Koike M, Shigihara N, Toyofuku Y, Ogihara T, Uchiyama Y, Yagihashi S, Fujitani Y, Watada H
    • Journal Title

      Endocrinology

      Volume: 154 Pages: 4512-4524

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of low-dose insulin on peripheral nerve insulin receptor signaling in streptozotocin-induced diabetic rats2013

    • Author(s)
      Sugimoto K, Baba M, Suzuki S, Yagihashi S.
    • Journal Title

      PLoS One

      Volume: 8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of long-term treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin on islet endocrine cells in non-obese type 2 diabetic Goto-Kakizaki rats2012

    • Author(s)
      Inaba W, Mizukami H, Kamata K, Takahashi K, Tsuboi K, Yagihashi S
    • Journal Title

      Eur J Pharmacol

      Volume: 691 Issue: 1-3 Pages: 297-306

    • DOI

      10.1016/j.ejphar.2012.07.030

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical staging of type 2 diabetes: The time has come2012

    • Author(s)
      Yagihashi S.
    • Journal Title

      J Diabetes Invest

      Volume: 3 Issue: 1 Pages: 1-2

    • DOI

      10.1111/j.2040-1124.2011.00192.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Augmented reduction of islet beta-cell mas in Goto-Kakizaki rats fed high fat diet and its suppression by pitavastatin treatment2012

    • Author(s)
      Mizukami H, Inaba W, Takahashi K, Inoue K, Sawanobori K, Yagihashi S
    • Journal Title

      J Diabetes Invest

      Volume: 3 Issue: 3 Pages: 235-244

    • DOI

      10.1111/j.2040-1124.2011.00173.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat2012

    • Author(s)
      Takahashi K, Mizukami H, Kamata K, Inaba W, Kato N, Hibi C, Yagihashi S
    • Journal Title

      PloS One

      Volume: 7 Issue: 1 Pages: e30134-e30134

    • DOI

      10.1371/journal.pone.0030134

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Imaging of insulin factory: Is it just imagination or approaching reality?2012

    • Author(s)
      Yagihashi S.
    • Journal Title

      J Diabetes Invest

      Volume: 3 Issue: 5 Pages: 429-31

    • DOI

      10.1111/j.2040-1124.2012.00236.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical staging od type 2 diabetes: The time has come.2012

    • Author(s)
      Soroku Yagihashi
    • Journal Title

      J Diabetes Invest

      Volume: 3(1)

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Imaging of insulin factory: Is it just imagination or approaching reality?2012

    • Author(s)
      Soroku Yagihashi
    • Journal Title

      J Diabetes Invest

      Volume: 3(5) Pages: 429-431

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Islet amyloid with macrophage migration correlates with augmented beta-cell deficits in type 2 diabetic patients2014

    • Author(s)
      Kamata K, Mizukami H, Inaba W, Takahashi K, Yagihashi S
    • Organizer
      American Diabetes Association Annual Meeting
    • Place of Presentation
      San Franscisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 日本人2型糖尿病の膵島アミロイド沈着と炎症反応2014

    • Author(s)
      鎌田耕輔、水上浩哉、稲葉渉、高橋一徳、八木橋操六
    • Organizer
      日本糖尿病学会総会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Annual Research Report
  • [Presentation] インクレチン関連薬使用糖尿病者の膵病理2014

    • Author(s)
      八木橋操六、水上浩哉、稲葉渉、坪井堅太郎
    • Organizer
      日本糖尿病学会総会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糖尿病性神経障害の成因と病態2014

    • Author(s)
      八木橋操六
    • Organizer
      日本糖尿病学会総会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 膵炎・膵臓がんの非臨床及び臨床評価(シンポジウム)2014

    • Author(s)
      八木橋操六
    • Organizer
      日本毒性学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖尿病性神経障害の成因の新たな展開2014

    • Author(s)
      水上浩哉、八木橋操六
    • Organizer
      日本糖尿病学会総会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Amelioration of neuropathic changes with correction of nerve insulin resistance in diabetic Goto-Kakizaki rats treated with DPP-IV inhibitor vildagliptin2013

    • Author(s)
      Tsuboi K, Mizukami H, Inaba W, Kamata K, Ogasawara S, Yagihashi S
    • Organizer
      49th Annual meeting of European Association of Study of Diabetes
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] Slow and minimal decline of beta cell mass associated with aging in non-diabetic Japanese and lack of compensatory islet hyperplasia in obesity2013

    • Author(s)
      Mizukami H, Takahashi K, Inaba W, Kamata K, Uehara O, Tsuboi K, Yagihashi S
    • Organizer
      49th Annual meeting of European Association of Study of Diabetes
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト2型糖尿病膵β細胞容積減少と酸化ストレス、ERストレス、オートファジーとの関連について2013

    • Author(s)
      吉田太郎、水上浩哉、稲葉渉、鎌田耕輔、坪井堅太郎、八木橋操六
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 網羅的メタボローム解析による新規糖尿病性神経障害発症機序の探索2013

    • Author(s)
      水上浩哉、坪井堅太郎、三五一憲、鎌田耕輔、稲葉渉、八木橋操六
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病病理学の進歩2013

    • Author(s)
      八木橋操六
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of DNA damage, ER-stress and autophagy deficits in the β cell loss in Japanese type 2 diabetic patients2013

    • Author(s)
      Iwashita M, Mizukami H, naba W, Osonoi S, Kamata K, Tsuboi K, Yagihashi S
    • Organizer
      56th Annual Meeting of Japan Diabetes Society
    • Place of Presentation
      Kumamoto
    • Related Report
      2013 Final Research Report
  • [Presentation] Progress and perspective of diabetic neuropathy care. New approach to the pathogenesis of diabetic polyneuropathy2013

    • Author(s)
      Mizukami H, Yagihashi S
    • Organizer
      56th Annual Meeting of Japan Diabetic Society
    • Place of Presentation
      Kumamoto
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of DNA damage, ER-stress and autophagy deficits in the b cell loss in Japanese type 2 diabetic patients2013

    • Author(s)
      Osonoi S, Mizukami H, Inaba W, Kamata K, Tsuboi K, Yagihashi S
    • Organizer
      73rd Annual Meeting of American Diabetes Association
    • Place of Presentation
      Chicago, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Metabolomic analysis of glycolytic pathway responsible for diabetic neuropathy beyond polyol pathway hyperactivity2013

    • Author(s)
      Mizukami H, Tsuboi K, Sango K, Chung SK, Yagihashi S
    • Organizer
      73rd Annual Meeting of American Diabetes Association
    • Place of Presentation
      Chicago, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 加齢、肥満によるヒト膵島容量変化の検討2012

    • Author(s)
      水上浩哉、高橋一徳、稲葉渉、鎌田耕輔、小笠原早織、八木橋操六
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      於京王プラザホテル
    • Related Report
      2013 Final Research Report
  • [Presentation] 網羅的メタボローム解析による糖尿病性神経障害の新しい発症機序の探索2012

    • Author(s)
      水上浩哉、坪井堅太郎、 三五一憲、鎌田耕輔、稲葉渉、八木橋操六
    • Organizer
      第56回日本糖尿病学会年次集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] Slow and progressive age-related decline of beta cell mass and proliferation activity of beta cells in non-diabetic Japanese subjects2012

    • Author(s)
      Mizukami H,Takahashi K, Inaba W, Kamata K, Tsuboi K, Yagihashi S
    • Organizer
      72nd Scientific Meeting if American Diabetes Assocation
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Amelioration of neuropathic changes with correction of nerve insulin resistance in diabetic Goto-Kakizaki rats treated with DPP-IV inhibitor, vildagliptin2012

    • Author(s)
      Tsuboi K, Mizukami H, Inaba W, KamataK, Ogasawara S, Yagihashi S
    • Organizer
      28th Annual Meeting of Neurodiab sutyd group
    • Place of Presentation
      Dresden, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Progressive age-related decline of beta cell mass and proliferation activity of beta cells in non-diabetic Japanese subjects2012

    • Author(s)
      Mizukami H, Takahashi K, Inaba W, Kamata K, Tsuboi K, Yagihashi S
    • Organizer
      72nd Scientific sessions of American Diabetes Association
    • Place of Presentation
      Philadelphia,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Preservation of islet beta cell mass with improvement of cell proliferation signals in GK rats treated with DPP-IV inhibitor.2012

    • Author(s)
      Kamata K, Mizukami H, Inaba W, Takahashi K, Yagihashi S
    • Organizer
      72nd Scientific sessions of American Diabetes Association
    • Place of Presentation
      Philadelphia,USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Is the skin biopsy useful to determine the severity of polyneuropathy in Japanese type 2 diabetic subjects?2012

    • Author(s)
      Yagihashi S, Murakami H, Sugimoto K, Uehara O, Tamasawa N, Murakami C, Baba M
    • Organizer
      22nd Annual Meeting of European Study Group of Diabetic Neuropathy
    • Place of Presentation
      Dresden,Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] Hexosamine pathway in the pathogenesis of diabetic neuropathy. Effects of glucosamine on the cultured Schwann cells2012

    • Author(s)
      Mizukami H, Tsuboi K, Kamata K, Takahashi K, Yagihashi S,
    • Organizer
      22nd Annual Meeting of European Study Group of Diabetic Neuropathy
    • Place of Presentation
      Dresden,Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] 糖尿病性神経障害研究の進歩2012

    • Author(s)
      八木橋操六
    • Organizer
      第27回日本糖尿病合併症学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Pathogenesis of diabetic neuropathy. Sugar or beyond sugar?2012

    • Author(s)
      Yagihashi S
    • Organizer
      9th International Diabetes Federation Asian and West Pacific Region Congress
    • Place of Presentation
      京都市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] 糖尿病神経障害.感覚運動神経障害.糖尿病最新の治療2013-2015(岩本安彦、羽田勝計、門脇孝編)2013

    • Author(s)
      八木橋操六(分担執筆)
    • Publisher
      南江堂、東京
    • Related Report
      2012 Research-status Report
  • [Book] 神経障害の疫学.ヴィジュアル糖尿病臨床のすべて.糖尿病予防と治療のエビデンス、荒木栄一、植木浩二郎編2012

    • Author(s)
      八木橋操六(分担執筆)
    • Publisher
      中山書店、東京、
    • Related Report
      2012 Research-status Report
  • [Book] 糖尿病性神経障害の発症機序.糖尿病学イラストレイテッド.春日雅人編2012

    • Author(s)
      八木橋操六
    • Publisher
      洋土社、東京
    • Related Report
      2012 Research-status Report
  • [Book] 糖尿病神経障害(多発神経障害と単神経障害)の病態について教えてください.循環器医から寄せられる「糖尿病と血管合併症」に関する100の質問、小室一成、山岸昌一編、2012

    • Author(s)
      八木橋操六
    • Publisher
      メディカルレビュー社、東京
    • Related Report
      2012 Research-status Report
  • [Book] 糖尿病性神経障害. 病気と薬.パーフェクトBook、薬局増刊号(横田千津子、池田宇一、大越教夫編)、2012

    • Author(s)
      杉本一博、八木橋操六
    • Publisher
      南山堂、東京
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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