2023 Fiscal Year Final Research Report
Exploring new pathway for the regulation of hepatic gluconeogenesis via microRNAs
| Project/Area Number |
20K08892
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2024-03-31
|
| Keywords | HMG-CoA還元酵素 / スタチン / 糖新生 / 糖尿病 / micro RNA |
|---|
| Outline of Final Research Achievements |
HMG-CoA reductase (HMGCR) and squalene synthase (SS) are the rate-limiting enzyme in the cholesterol synthesis pathway. We showed that liver-specific HMGCR (L-HMGCR) or SS gene knockout mice exhibited low blood glucose with liver injury 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 miR-96/182/183 was induced in the liver of L-HMGCR knockout and it may reduce the genes for hepatic glucose production.
|
| Free Research Field |
diabetes
|
| 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、この機序として、あるmicroRNAクラスターの高発現が肝糖新生を抑制させた可能性を示した。これは新たな糖新生抑制経路の発見、さらには新たな糖尿病治療薬の開発につながる研究成果であり社会的意義は大きいと考えられる。
|
