| Project/Area Number |
17K09718
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kanazawa Medical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
古家 大祐 金沢医科大学, 医学部, 教授 (70242980)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 糖尿病性腎臓病 / 2型糖尿病ラット / 低蛋白質食 / メチオニン / S-アデノシルメチオニン / オートファジー / グリシンNメチルトランスフェラーゼ / 糖尿病性腎症 / mTOR1 / 糖尿病腎症 / 糖尿病 |
|---|
| Outline of Final Research Achievements |
A low-protein diet (LPD) exerts the renoprotective effect through the suppression of mechanistic target of rapamycin complex 1 (mTORC1) and improvement of autophagy in Wistar fatty (fa/fa) rats (WFRs), type 2 diabetes/obesity. Results of metabolome analysis in blood of rats demonstrated that the levels of S-adenosylmethionine (SAM), metabolite of methionine (Met), is clearly increased in the blood of WFRs compared to non-diabetic control rats, and a LPD decreases it. In addition, the expression of glycine-N-methyltransferase (Gnmt), which is the main metabolic enzyme for SAM, is significantly decreased in the WFRs, compared to non-diabetic control rats. In the present study, we found that the addition of Met with the LPD abrogates the beneficial effects induced by the LPD in diabetic kidney. A LPD could exert a renoprotective effect through the suppression of mTORC1 and restoration of autophagy, which is associated with reduced levels of SAM due to low-Met intake, in diabetic kidney.
|
| Academic Significance and Societal Importance of the Research Achievements |
臨床上,低蛋白質食は糖尿病性腎臓病を含む慢性腎臓病抑制の為の食事療法であるが,不適切な低蛋白質食は,蛋白質-エネルギバランスの不均衡やサルコペニアなどの栄養障害の危険を伴う.低メチオニン食や,メチオニン含有量が豊富な赤身肉などの動物性蛋白質の回避は,低蛋白質食の栄養障害の危険の軽減とともに低蛋白質食代替え食となる可能性がある. 低メチオニン食は,健康的な代謝の維持,心血管疾患の抑制などの利点を提供することに加えて,糖尿病性腎臓病を有する2型糖尿病患者とっての新規食事療法となり得る. しかし低メチオニン食がヒトの糖尿病性腎臓病を抑制できるかについては更なる研究が必要である.
|
