IRS1/insulin signaling-induced repair mechanisms of podocyte injury
| Project/Area Number |
26461230
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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 |
Kidney internal medicine
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| Research Institution | Kindai University |
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Principal Investigator |
MIMA Akira 近畿大学, 医学部附属病院, 講師 (00432401)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | インスリンシグナル / ポドサイトアポトーシス / IRS1 / 糖尿病性腎症 / インスリン受容体基質 |
|---|
| Outline of Final Research Achievements |
Immunoblot analyses showed insulin (10nM) increased the levels of phosphorylation of Akt (pAkt) which had anti-apoptotic effects by 4.5±0.7-fold. In contrast, high glucose (HG; 20mM) levels decreased the expression by 7.8%. Insulin increased tyrosine phosphorylation of insulin substrate (IRS)1 by 2-fold in low glucose (LG; 5.6mM), while HG decreased the expression by 10%. Infection with IRS1 using adenoviral vector (Ad-IRS1) decreased HG-induced podocyte apoptosis by 57%. To assess the role of IRS1 in mediating the podocyte apoptosis, IRS1 expression was reduced with siIRS1. Knockdown of IRS1 in podocytes increased apoptosis by 2.4±0.4-fold. Lastly, DPP-4 inhibitor increased the levels of pAkt by 131±28%. These results suggest that increases in insulin signaling activity in podocytes using Ad-IRS1 or DPP-4i could inhibit HG-induced podocyte apoptosis.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance2016
Author(s)
Katagiri S, Park K, Maeda Y, Rao TN, Khamaisi M, Li Q, Yokomizo H, Mima A, Lancerotto L, Wagers A, Orgill DP, King GL
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Journal Title
Diabetes
Volume: 65
Issue: 9
Pages: 2760-2771
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Insulin decreases atherosclerosis by inducing endothelin receptor B expression2016
Author(s)
Park K, Mima A, Li Q, Rask-Madsen C, He P, Mizutani K, Katagiri S, Maeda Y, Wu IH, Khamaisi M, Preil SR, Maddaloni E, Sorensen D, Rasmussen LM, Huang PL, King GL
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Journal Title
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LCAPの返血時に返血側を加温することで鋭い血管痛が消失した1症例2016
Author(s)
左官 真以子, 川崎 広樹, 西辻 冬馬, 津川 真伍, 高儀 良平, 末野 優史, 小山 和彦, 植田 隆介, 堀 辰之, 小木 幸人, 丹正 幸佑, 長原 大, 美馬 晶
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Journal Title
日本アフェレシス学会雑誌
Volume: 35
Pages: 179-179
Related Report
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[Journal Article] 奈良県における慢性透析患者の現況 2014年12月末の統計的観察2016
Author(s)
米田 龍生, 吉田 克法, 平尾 佳彦, 斎藤 能彦, 柏井 浩希, 丘田 英人, 三馬 省二, 熊本 廣実, 青山 秀雄, 松原 博, 松本 宗輔, 金子 佳照, 吉岡 伸夫, 枝川 光太郎, 枝川 篤永, 森田 壮平, 阿部 泰志, 松田 尚史, 田中 正己, 美馬 晶
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Journal Title
奈良県医師会透析部会誌
Volume: 21
Pages: 21-27
NAID
Related Report
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[Journal Article] Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.2015
Author(s)
Matsubara T, Araki M, Abe H, Ueda O, Jishage K, Mima A, Goto C, Tominaga T, Kinosaki M, Kishi S, Nagai K, Iehara N, Fukushima N, Kita T, Arai H, Doi T.
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Journal Title
Diabetes
Volume: ６４
Issue: 8
Pages: 2978-2990
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Hemodialysis Vascular Access Complications2015
Author(s)
Akira Mima
Organizer
Launching Ceremony and the Scientific Congress of Ho Chi Minh City Society of Dialysis Therapies (HSDT), the CME Course on Nephrology and Dialysis, and the 1st Congress of the HSDT
Place of Presentation
ベトナム、ホーチミン
Year and Date
2015-12-26
Related Report
Int'l Joint Research / Invited
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