Elucidation of molecular mechanisms on macrophage infiltration into pancreatic islets in type 2 diabetes and challenging trial to establish its preventive strategy.
| Project/Area Number |
25461363
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INUKAI Koichi 杏林大学, 医学部, 准教授 (20333007)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 2型糖尿病 / マクロファージ / 膵β細胞 / 脂肪細胞 / MCP-1 / 内因性酸化ストレス / Astaxanthin / JNK経路 / ２型糖尿病 / 脂肪脂肪 / VEGF / PI3K依存性経路 |
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| Outline of Final Research Achievements |
We analyzed the influence of antioxidant astaxanthin on monocyte chemoattractant protein-1 (MCP-1), a key factor on free fatty acids-induced chronic inflammation, by using mouse insulinoma (MIN6) cells long-term treated with high concentration of palmitate. While palmitate significantly increased endogenous oxidative stress and enhanced MCP-1 secretion in MIN6 cells, astaxanthin as well as SP600125, a JNK-specific inhibitor, clearly reduced this enhanced MCP-1. Furthermore, astaxanthin attenuated JNK phosphorylation, and also diminished endoplasmic reticulum stress enhanced by palmitate.
Taken together, astaxanthin can suppress MCP-1 release, which is up-regulated by palmitate, through the inactivity of JNK pathways on MIN6 cells. The results of this study raise the possibility that astaxanthin would become a new preventive tool for the progression of β cell dysfunction observed in type 2 diabetes with clinical dyslipidemia.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals2015
Author(s)
H.Katsuta, S.Ozawa, K.Suzuki, K.Takahashi, T.Tanaka, Y.Sumitani, S.Nishida, T.Kondo, T.Hosaka, and H.Ishida.
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Journal Title
Endocrine Journal
Volume: 62
Issue: 6
Pages: 485-492
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed
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[Journal Article] Ghrelin augments the expressions and secretions of proinflammatory adipokines, VEGF120 and MCP-1, in differentiated 3T3-L1 adipocytes.2015
Author(s)
A. Kitahara, K. Takahashi, R. Moriya, H. Onuma, K. Handa, Y. Sumitani, T. Tanaka, H. Katsuta, S. Nishida, T. Sakurai, K. Inukai, H. Ohno, and H. Ishida.
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Journal Title
J Cell Physiol
Volume: 230
Issue: 1
Pages: 199-209
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term low carbohydrate diet leads to deleterious metabolic manifestations in diabetic mice.2014
Author(s)
Handa K, Inukai K, Onuma H, Kudo A, Nakagawa F, Tsuruga K, Kitahara A, Moriya R, Takahashi K, Sumitani Y, Hosaka T, Kawakami H, Oyadomari S, Ishida H
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Journal Title
PLoS One
Volume: 9
Issue: 8
Pages: 104948-104948
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Enzyme-treated asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence-accelerated mice.2014
Author(s)
T. Sakurai, T. Ito, K.Wakame, K. Kitadate, T.Arai, J. Ogasawara, T. Kizaki, S.Sato, Y.Ishibashi,T.Fujiwara, K.Akagawa H. Ishida, and H. Ohno.
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Journal Title
Natural Product Commun
Volume: 9(1)
Pages: 101-106
Related Report
Peer Reviewed
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[Journal Article] Possible involvement of PI3K-dependent pathways in the increased VEGF120 release from osteoblastic cells preloaded with palmitate.2014
Author(s)
R. Moriya, K. Takahashi, A. Kitahara, H. Onuma, K. Handa, Y. Sumitani, T. Tanaka, H.Katsuta, S. Nishida, E. Itagaki, K. Inukai, and H. Ishida.
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Journal Title
Biochem Biophys Res Commun
Volume: 445
Issue: 2
Pages: 275-281
DOI
Related Report
Peer Reviewed
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[Presentation] VEGF120 secretion from palmitate-preloaded osteoblastic cells is enhanced through the activation of PI3K-dependent pathways.2014
Author(s)
Moriya R, Takahashi K, Kitahara A, Onuma H, Handa K, Sumitani Y, Tanaka T, Katsuta H, Nishida S, Itagaki E, Inukai K, Ishida H
Organizer
The American Diabetes Association's 73nd Scientific Sessions,
Place of Presentation
San Francisco, USA
Year and Date
2014-06-13 – 2014-06-17
Related Report
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[Presentation] Direct action of ghrelin enhance the secretions of proinflammatory adipokines from mature 3T3-L1 adipcocytes in vitro.2014
Author(s)
Kitahara A, Takahashi K, Moriya R, Onuma H, Handa K, Sumitani Y, Tanaka T, Katsuta H, Nishida S, Sakurai T, Inukai K, Ohno H, Ishida H
Organizer
The American Diabetes Association's 73nd Scientific Sessions,
Place of Presentation
San Francisco, USA
Year and Date
2014-06-13 – 2014-06-17
Related Report
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