Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context
Summary: Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulati...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422005242 |
| _version_ | 1811179708276015104 |
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| author | Futoshi Furuya Yoshihito Fujita Naomi Matsuo Hiroto Minamino Yasuo Oguri Nozomi Isomura Kaori Ikeda Kohei Takesue Ying Li Aki Kondo Fumika Mano Nobuya Inagaki |
| author_facet | Futoshi Furuya Yoshihito Fujita Naomi Matsuo Hiroto Minamino Yasuo Oguri Nozomi Isomura Kaori Ikeda Kohei Takesue Ying Li Aki Kondo Fumika Mano Nobuya Inagaki |
| author_sort | Futoshi Furuya |
| collection | DOAJ |
| description | Summary: Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulation of energy metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear. Methods: We investigated the factors associated with the beneficial effects of dapagliflozin, a SGLT2 inhibitor, in the liver after confirming its glucose-lowering and weight loss effects using an obesity and diabetes mouse model. We also performed clinical study of patients with type 2 diabetes to explore candidate biomarkers that reflect the beneficial action of dapagliflozin in the liver. Findings: In animal study, dapagliflozin induced autophagy in the liver (LC3-II to LC3-I expression ratio: P < 0·05 vs. control), and valine and leucine levels were increased in plasma (P < 0·01 vs. control) as well as in liver (P < 0·05 vs. control). Thus, increased plasma valine and leucine levels are potential biomarkers for improved liver metabolism. Clinical study found that valine and leucine levels were markedly higher in patients treated with dapagliflozin (valine: P < 0·05 vs. control, leucine: P < 0·01 vs. control) than those not treated after one week intervention. Interpretation: Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine and leucine levels may reflect its metabolic effect. Funding: AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), Novo Nordisk Pharma Ltd., and Japan Foundation for Applied Enzymology, and MSD Life Science Foundation International. |
| first_indexed | 2024-04-11T06:38:01Z |
| format | Article |
| id | doaj.art-53756e734db4494697f810791fc22211 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-11T06:38:01Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-53756e734db4494697f810791fc222112022-12-22T04:39:37ZengElsevierEBioMedicine2352-39642022-12-0186104342Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in contextFutoshi Furuya0Yoshihito Fujita1Naomi Matsuo2Hiroto Minamino3Yasuo Oguri4Nozomi Isomura5Kaori Ikeda6Kohei Takesue7Ying Li8Aki Kondo9Fumika Mano10Nobuya Inagaki11Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanCorresponding author. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanCorresponding author. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanSummary: Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulation of energy metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear. Methods: We investigated the factors associated with the beneficial effects of dapagliflozin, a SGLT2 inhibitor, in the liver after confirming its glucose-lowering and weight loss effects using an obesity and diabetes mouse model. We also performed clinical study of patients with type 2 diabetes to explore candidate biomarkers that reflect the beneficial action of dapagliflozin in the liver. Findings: In animal study, dapagliflozin induced autophagy in the liver (LC3-II to LC3-I expression ratio: P < 0·05 vs. control), and valine and leucine levels were increased in plasma (P < 0·01 vs. control) as well as in liver (P < 0·05 vs. control). Thus, increased plasma valine and leucine levels are potential biomarkers for improved liver metabolism. Clinical study found that valine and leucine levels were markedly higher in patients treated with dapagliflozin (valine: P < 0·05 vs. control, leucine: P < 0·01 vs. control) than those not treated after one week intervention. Interpretation: Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine and leucine levels may reflect its metabolic effect. Funding: AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), Novo Nordisk Pharma Ltd., and Japan Foundation for Applied Enzymology, and MSD Life Science Foundation International.http://www.sciencedirect.com/science/article/pii/S2352396422005242Sodium glucose co-transporter 2 (SGLT2) inhibitorDiabetesLiverAutophagyBranched chain amino acids (BCAAs)Biomarker |
| spellingShingle | Futoshi Furuya Yoshihito Fujita Naomi Matsuo Hiroto Minamino Yasuo Oguri Nozomi Isomura Kaori Ikeda Kohei Takesue Ying Li Aki Kondo Fumika Mano Nobuya Inagaki Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context EBioMedicine Sodium glucose co-transporter 2 (SGLT2) inhibitor Diabetes Liver Autophagy Branched chain amino acids (BCAAs) Biomarker |
| title | Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context |
| title_full | Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context |
| title_fullStr | Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context |
| title_full_unstemmed | Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context |
| title_short | Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozinResearch in context |
| title_sort | liver autophagy induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co transporter 2 inhibitor dapagliflozinresearch in context |
| topic | Sodium glucose co-transporter 2 (SGLT2) inhibitor Diabetes Liver Autophagy Branched chain amino acids (BCAAs) Biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422005242 |
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