The significance of selective insulin resistance in kidney for hypertension and renal insufficiency.
Project/Area Number |
24591225
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | The University of Tokyo |
Principal Investigator |
SUZUKI Masashi 東京大学, 医学部附属病院, 特任講師 (90595662)
|
Co-Investigator(Kenkyū-buntansha) |
SEKI George 東京大学, 医学部附属病院, 講師 (30206619)
YAMADA Hideomi 東京大学, 医学部附属病院, 講師 (60396752)
HORITA Shoko 東京大学, 医学部附属病院, 講師 (20534895)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 高血圧 / インスリン抵抗性 / メタボリック症候群 |
Outline of Final Research Achievements |
Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on adipocytes and proximal tubules in rats and humans. The stimulatory effect of insulin on NBCe1 activity via IRS2 pathway and IRS2 expression in the kidney cortex were exceptionally preserved in both rats and humans with insulin resistance. Unlike liver, acute insulin injection failed to change the expression levels of IRS2 and sterol regulatory element-binding protein 1 in rat kidney cortex, indicating that regulatory mechanisms of IRS2 expression are distinct in liver and kidney. Thus, preserved stimulation of proximal tubule transport through the insulin/IRS2/PI3-K pathway may play an important role in the pathogenesis of hypertension associated with metabolic syndrome.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome.2015
Author(s)
Nakamura M, Yamazaki O, Shirai A, Horita S, Satoh N, Suzuki M, Hamasaki Y, Noiri E, Kume H, Enomoto Y, Homma Y, Seki G
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Journal Title
Kidney Int.
Volume: 87
Issue: 3
Pages: 535-542
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3',5'-Cyclic Monophosphate Pathway.2014
Author(s)
Shirai A, Yamazaki O, Horita S, Nakamura M, Satoh N, Yamada H, Suzuki M, Kudo A, Kawakami H, Hofmann F, Nishiyama A, Kume H, Enomoto Y, Homma Y, Seki G.
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Journal Title
J Am Soc Nephrol
Volume: 未定
Issue: 7
Pages: 1523-1532
DOI
Related Report
Peer Reviewed
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[Journal Article] Mutation of the renal Mg2+ transporter SLC41A1 in a nephronophthisis-like phenotype.2013
Author(s)
Hurd TW, Edgar Otto EA, Mishima E, Gee HY, Hana Inoue4, Inazu M, Yamada H, Halbritter J, Seki G, Konishi M, Zhou W, Yamane T, Murakami S, Caridi G, Ghiggeri G, Abe T, Hildeb F.
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Journal Title
J Am Soc Nephrol
Volume: 未定
Related Report
Peer Reviewed
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[Journal Article] Irbit Mediates Synergy Between Ca2+ and cAMP Signaling Pathways During Epithelial Transport in Mice.2013
Author(s)
Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S
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Journal Title
Gastroenterology
Volume: S0016-5085(13)
Issue: 1
Pages: 232-241
DOI
Related Report
Peer Reviewed
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