Analysis of islet remodeling in type 2 diabetes and exploratory regulation of endocrine cell transdifferentiation (metaplasia)
| Project/Area Number |
16K09771
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | The Nukada Institute for Medical & Biological Research |
|---|
Principal Investigator |
Yagihashi Soroku 公益財団法人額田医学生物学研究所, その他部局等, その他 (40111231)
|
|---|
| Research Collaborator |
Mizukami Hiroki
Nukada Hitoshi
Hotta Ryotarou
Ogasawara Saori
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 2型糖尿病 / 膵島 / アミロイド / 病理 / インスリン抵抗性 / 内分泌細胞分化 / β細胞 / ホルモン陰性内分泌細胞 / α細胞 / 膵ランゲルハンス島 / 分化転換 / 治療 / 細胞変換（化生） / 糖尿病治療 / インスリン / グルカゴンン / ソマトスタチン / 糖尿病 / 発生・分化 / トランスレーショナルリサーチ / 内科 / 細胞・組織 |
|---|
| Outline of Final Research Achievements |
Islet pathology in human type 2 diabetes is exemplified by beta-cell depletion and relative alpha-cell expansion as well as amyloid deposition. It is yet to be clear how these changes reflect clinical profile or predict the prognosis. In this study, we studied islet amyloid deposition and endocrine cell composition in 60 autopsy cases with type 2 diabetes and their correlation with clinical parameters. Islet pathology was morphometrically analyzed on pancreas sections stained with thioflavin to identify amyloid or with immunostains for endocrine cell discrimination. As results, amyloid deposition was associated with augmented reduction of both beta-cells and alpha-cells with impaired remodeling of islet endocrine cells. It was thus suggested that amyloid deposition destroyed islet microenvironment and compromised reserved capacity of the islet, worsening diabetes with resultant poor prognosis.
|
| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、日本人2型糖尿病の膵島でのアミロイド沈着が膵島リモデリングによる病態修復機構を干渉し、糖尿病病態を悪化、進展させている可能性が示された。脂質異常やインスリン抵抗性はアミロイド沈着と密接に関連しており、その抑制は糖尿病進展の抑制へとつながる。今回の研究成果は、2型糖尿病の新しい治療方向として、糖・脂質代謝と関連するインスリン抵抗性の改善、アミロイド沈着抑制による膵島微小環境の保護など有益である可能性を示すものである。
|
Report
(4 results)
Research Products
(35 results)
-
-
-
-
-
[Journal Article] A spontaneously immortalized Schwann cell line from aldose reductase-deficient mice as a useful tool for studying polyol pathway and aldehyde metabolism.2018
Author(s)
Niimi N, Yako H, Takaku S, Kato H, Matsumoto T, Nishito Y, Watabe K, Ogasawara S, Mizukami H, Yagihashi S, Chung SK, Sango K.
-
Journal Title
J Neurochem
Volume: 144
Issue: 6
Pages: 710-722
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Worsened outcome in patients with pancreatic ductal carcinoma on long-term diabetes: association with E-cadherin1 (CDH1) promoter methylation.2017
Author(s)
Saito T, Mizukami H, Umetsu S, Uchida C, Inaba W, Abe M, Takahashi K, Kudo K, Itabashi C, Yagihashi S, Hakamada K.
-
Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 18056-18067
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Four-year sequential nerve conduction changes since first visit in Japanese patients with early type 2 diabetes.2017
Author(s)
Kobori M, Yagihashi S, Shiina N, Shiozawa N, Haginoya A, Ojima M, Douguchi S, Tamasawa A, Saitou M, Baba M, Osonoi T.
-
Journal Title
J Diabetes Investig
Volume: 8
Issue: 3
Pages: 369-376
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
