The role of insulin signaling pathway on the development of diabetic nephropathy
| Project/Area Number |
26670455
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Kaburagi Yasushi 国立研究開発法人国立国際医療研究センター, その他部局等, 臓器障害研究部長 (40342927)
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| Co-Investigator(Kenkyū-buntansha) |
久保田 浩之 (卯木浩之 / 久保田 浩之(卯木浩之)) 国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (40323290)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 糸球体上皮細胞 / インスリンシグナル伝達系 / 糖尿病腎症 |
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| Outline of Final Research Achievements |
In this study, we examined the role of insulin signaling pathway in podocytes on the development of diabetic nephropathy. The podocyte-specific knock-out mice were generated using the Cre-mediated recombination controlled by the podocin promoter. Knock-out mice was developed proteinuria around 3 week-old age, and died due to end stage renal failure by 10 weeks after birth. Histologically, features characteristic of focal segmental glomerular sclerosis, including podocyte foot process effacement, mesangial sclerosis, and casts, were observed in the kidney of knock-out mice. Podocytes isolated from knockout-mice also exhibited the lowered autophagic activity as indicated by an increased abundance of p62 and a decreased abundance of LC3B-II. These findings suggest that dysregulation of insulin signaling pathway in podocytes may be involved in the pathogenesis of podocyte injury, leading to proteinuric kidney disease.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.2017
Author(s)
Takahashi E, Unoki-Kubota H, Shimizu Y, Okamura T, Iwata W, Kajio H, Yamamoto-Honda R, Shiga T, Yamashita S, Tobe K, Okumura A, Matsumoto M, Yasuda K, Noda M, Kaburagi Y.
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Journal Title
J Diabetes Investig.
Volume: 印刷中
Issue: 5
Pages: 661-671
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch.2016
Author(s)
Sakai M, Tujimura-Hayakawa T, Yagi T, Yano H, Mitsushima M, Unoki-Kubota H, Kaburagi Y, Inoue H, Kido Y, Kasuga M, Matsumoto M.
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Journal Title
Nat Commun.
Volume: 7
Issue: 1
Pages: 13147-13147
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduced serum levels of leukocyte cell-derived chemotaxin 2 are associated with the presence of diabetic retinopathy2016
Author(s)
Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko, Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
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Journal Title
Clinica Chimica Acta
Volume: 463
Pages: 145-149
DOI
Related Report
Peer Reviewed
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