2023 Fiscal Year Final Research Report
Elucidating the mechanisms by which SGLT2 inhibitors regulate systemic metabolism via gluconeogenesis
| Project/Area Number |
22K16421
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 糖新生 / 糖尿病 / 肥満 |
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| Outline of Final Research Achievements |
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a type of drug used to treat diabetes, lower blood sugar by excreting sugar in the urine. When blood sugar levels fall, glycogen breakdown is followed by the activation of gluconeogenesis. Gluconeogenesis uses glycerol and amino acids supplied from fat and muscle as substrates, and gluconeogenesis is carried out via metabolic pathways mediated by the gluconeogenic enzymes GYK and PEPCK, respectively.
When SGLT2 inhibitors were administered to liver-specific GYK-deficient, liver-specific PEPCK-deficient and kidney-specific PEPCK-deficient mice, changes in body weight, fat mass and muscle mass were characterized according to the deficient glycogenic enzyme.
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| Free Research Field |
糖代謝
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果として、欠損する糖新生酵素によって、SGLT2阻害薬によるエネルギー喪失が引き起こす臓器毎の影響が異なることが確認された。SGLT2阻害薬投与による脂肪や筋肉の分解のメカニズムの解明が進むことで、肥満症やサルコペニア肥満の治療や予防の開発につながりうることが期待される。
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