Molecular mechanisms of disorder of pancreatic beta cells induced by excess selenoprotein P
| Project/Area Number |
17H03821
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Food science
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
Saito Yoshiro 東北大学, 薬学研究科, 教授 (70357060)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|
|---|
| Keywords | セレン / 膵β細胞 / インスリン分泌 / 小胞体ストレス / 膵肝代謝制御 / フェロトーシス / アポトーシス / リポプロテイン受容体 / インスリン / 親電子物質 / 発現制御 / 2型糖尿病 / セレノプロテイン / 糖尿病 / 中和抗体 / 疾患モデルマウス / 栄養学 / 食品 / 細胞・組織 |
|---|
| Outline of Final Research Achievements |
Selenoprotein P (SeP), a plasma protein containing essential trace element selenium, functions as a transporter of selenium, delivering selenium to the cells. We found the increase of SeP levels in type 2 diabetes patients and have reported that increased SeP (excess SeP) worsen glucose metabolism via the increase of insulin resistance in the skeletal muscle and liver. In the present study, we found that excess SeP is incorporated into the pancreatic beta cells via SeP receptors and decreases insulin secretion via ER stress. Furthermore, we found the physiological role of SeP expression in the pancreatic beta cells and stated the novel metabolism regulation between the pancreas and liver via insulin and SeP.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、膵β細胞の機能を制御する新たな機構が明らかとなり、膵β細胞を保護し、2型糖尿病を治療する新たな戦略が見いだされた。さらに、膵β細胞におけるSeP発現の意義、およびインスリンを介したSeP発現制御機構が見いだされ、分泌因子を介した密接な膵肝代謝制御機構が明らかとなった。本研究成果をさらに進展することで、未だ開発されていない膵機能保護薬の開発が実現できると確信する。
|
Report
(4 results)
Research Products
(48 results)
-
-
-
-
-
[Journal Article] Circulating Concentrations of Insulin Resistance-Associated Hepatokines, Selenoprotein P and Leukocyte Cell-Derived Chemotaxin 2, during an Oral Glucose Tolerance Test in Humans2019
Author(s)
Mohri K, Misu H, Takayama H, Ishii KA, Kikuchi A, Lan F, Enyama Y, Takeshita Y, Saito Y, Kaneko S,Takamura T.
-
Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 3
Pages: 373-378
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-03-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Diagnostic and Prognostic Significance of Serum Levels of SeP (Selenoprotein P) in Patients With Pulmonary Hypertension2019
Author(s)
Nobuhiro Kikuchi, Kimio Satoh, Taijyu Satoh, Nobuhiro Yaoita, Mohammad Abdul Hai Siddique, Junichi Omura, Ryo Kurosawa, Masamichi Nogi, Shinichiro Sunamura, Satoshi Miyata, Hirofumi Misu, Yoshiro Saito, Hiroaki Shimokawa
-
Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 39
Issue: 12
Pages: 2553-2562
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.2018
Author(s)
Oo SM, Misu H, Saito Y, Tanaka M, Kato S, Kita Y, Takayama H, Takeshita Y, Kanamori T, Nagano T, Nakagen M, Urabe T, Matsuyama N, Kaneko S, Takamura T.
-
Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 16727-16727
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Selenoprotein P Promotes the Development of Pulmonary Arterial Hypertension.2018
Author(s)
Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Elias-Al-Mamun M, Siddique MAH, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Saito Y, Hoshikawa Y, Okada Y, Shimokawa H.
-
Journal Title
Circulation
Volume: 138
Issue: 6
Pages: 600-623
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy2018
Author(s)
Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K.
-
Journal Title
Genes to Cells
Volume: 23
Issue: 1
Pages: 22-34
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Diagnosis of Parkinson's disease and the level of oxidized DJ-1 protein.2018
Author(s)
Yamagishi Y, Saigoh K, Saito Y, Ogawa I, Mitsui Y, Hamada Y, Samukawa M, Suzuki H, Kuwahara M, Hirano M, Noguchi N, Kusunoki S.
-
Journal Title
Neurosci Res.
Volume: なし
Pages: 58-62
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Eicosapentaenoic acid down-regulates expression of the selenoprotein P gene by inhibiting SREBP-1c protein independently of the AMP-activated protein kinase pathway in H4IIEC3 hepatocytes.2017
Author(s)
Tajima-Shirasaki N, Ishii KA, Takayama H, Shirasaki T, Iwama H, Chikamoto K, Saito Y, Iwasaki Y, Teraguchi A, Lan F, Kikuchi A, Takeshita Y, Murao K, Matsugo S, Kaneko S, Misu H, Takamura T.
-
Journal Title
J Biol Chem.
Volume: 292
Issue: 26
Pages: 10791-10800
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
