| Project/Area Number |
17K09683
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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 | Akita University |
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Principal Investigator |
FUJITA HIROKI 秋田大学, 医学系研究科, 准教授 (30333933)
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| Co-Investigator(Kenkyū-buntansha) |
山田 祐一郎 秋田大学, 医学系研究科, 教授 (60283610)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 糖尿病性腎症 / インクレチン / GIP / 内科 |
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| Outline of Final Research Achievements |
We investigated whether increased GIP receptor signaling provides protective effects in diabetic kidneys. Through the analysis in diabetic nephropathy-resistant C57BL/6-Akita mice, we found that GIP receptor-deficient C57BL/6-Akita mice which have reduced GIP receptor signaling exhibit increased albuminuria, glomerulosclerosis and oxidative stress. Unexpectedly, GIP administration did not ameliorate diabetic renal injury in KK/Ta Akita mice which develop progressive diabetic nephropathy. The RT-PCR analysis revealed that GIP receptor is poorly expressed in mouse kidneys as compared with the receptor of another gut incretin hormone GLP-1. Taken together, these findings suggest that the administration of GIP alone does not highly exert renal protective effects in progressive diabetic nephropathy. However, considering that GIP and GLP-1 have an anti-oxidative effect, the administration of GIP in addition to GLP-1 may provide additive protective effects in diabetic kidneys.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病腎において、2つの主要なインクレチンGLP-1とGIPはともに抗酸化作用を介して腎保護的に働いてはいるが、腎臓内ではGLP-1受容体シグナルの方が中心となって腎保護の役割を担っていることが明らかとなった。GLP-1とGIPの併用療法による糖尿病腎における相加的腎保護効果の可能性が期待されることから、糖尿病性腎症に対する新たな治療戦略としての確立を目指し、今後さらなる研究を遂行していく必要がある。
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