Reduction of hepatic cholesterol synthesis is associated with hepatic glucose production
| Project/Area Number |
17K09865
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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 |
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | HMG-CoA還元酵素 / スタチン / 糖尿病 / micro RNA / 遺伝子改変動物 / 肝糖新生 / 肝細胞 / 肝臓 / 糖新生 / マイクロRNA / 低血糖 / コレステロール合成経路 / 血糖低下 / スクアレン合成酵素 |
|---|
| Outline of Final Research Achievements |
HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the cholesterol synthesis pathway. HMGCR inhibitors, statins, which are used to prevent cardiovascular diseases, have propensity to induce hyperglycemia. On the other hand, we showed that liver-specific HMGCR gene knockout (L-KO) mice exhibited low blood glucose and genes associated with hepatic glucose production were decreased in the liver. To investigate the role of HMGCR in the hepatic glucose production, we used the RNA-sequencing technology which can generate comprehensive transcriptomic information. We found out that one microRNA cluster in the liver of L-KO was induced and it may reduce the genes for hepatic glucose production.
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| Academic Significance and Societal Importance of the Research Achievements |
コレステロール合成経路を抑制するHMG-CoA還元酵素(HMGCR)阻害薬スタチンによって、耐糖能が悪化することが明らかになっており、コレステロール代謝と糖代謝 の関連性が注目されている。この一方で、我々はコレステロール合成を肝臓で抑制すると血糖が低下し、これには肝糖新生の低下が関与していることを示した。スタチンによる耐糖能悪化を予防し、さらには糖新生抑制という観点から新たな糖尿病治療薬の開発につながる研究成果が得られた社会的意義は大きいと考えられる。
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Report
(5 results)
Research Products
(10 results)
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[Journal Article] β-Cell-specific deletion of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase causes overt diabetes due to reduction of β-cell mass and impaired insulin secretion.2020
Author(s)
Takei Shoko, Nagashima Shuichi, Takei Akihito, Yamamuro Daisuke, Wakabayashi Tetsuji, Murakami Akiko, Isoda Masayo, Yamazaki Hisataka, Ebihara Chihiro, Takahashi Manabu, Ebihara Ken, Dezaki Katsuya, Takayanagi Yuki, Onaka Tatsushi, Fujiwara Ken, Yashiro Takashi, Ishibashi Shun
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Journal Title
Diabetes
Volume: 69
Issue: 11
Pages: 2352-2363
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice2020
Author(s)
Takei A, Nagashima S, Takei S, Yamamuro D, Murakami A, Wakabayashi T, Isoda M, Yamazaki H, Ebihara C, Takahashi M, Ebihara K, Ishibashi S
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Journal Title
Diabetes
Volume: 69
Pages: 158-164
Related Report
Peer Reviewed / Open Access
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