Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications
Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to β-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/5/726 |
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| author | Hidekatsu Yanai Hiroki Adachi Mariko Hakoshima Hisayuki Katsuyama |
| author_facet | Hidekatsu Yanai Hiroki Adachi Mariko Hakoshima Hisayuki Katsuyama |
| author_sort | Hidekatsu Yanai |
| collection | DOAJ |
| description | Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to β-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen species production, improves mitochondrial function and integrity, and also improves the structure and function of endoplasmic reticulum (ER), changes which enhance glucose-stimulated insulin secretion and inhibit the apoptosis of β-cells, leading to β-cell mass preservation. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. Clinical trials into the effects of imeglimin monotherapy and combination therapy exhibited an excellent hypoglycemic efficacy and safety profile in type 2 diabetic patients. Mitochondrial impairment is closely associated with endothelial dysfunction, which is a very early event in atherosclerosis. Imeglimin improved endothelial dysfunction in patients with type 2 diabetes via both glycemic control-dependent and -independent mechanisms. In experimental animals, imeglimin improved cardiac and kidney function via an improvement in mitochondrial and ER function or/and an improvement in endothelial function. Furthermore, imeglimin reduced ischemia-induced brain damage. In addition to glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients. |
| first_indexed | 2024-03-11T03:55:50Z |
| format | Article |
| id | doaj.art-8cbd5d68fd9740bb8241a6e0b467e662 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T03:55:50Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-8cbd5d68fd9740bb8241a6e0b467e6622023-11-18T00:33:32ZengMDPI AGBiology2079-77372023-05-0112572610.3390/biology12050726Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic ComplicationsHidekatsu Yanai0Hiroki Adachi1Mariko Hakoshima2Hisayuki Katsuyama3Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, JapanDepartment of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, JapanDepartment of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, JapanDepartment of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, JapanMitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to β-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen species production, improves mitochondrial function and integrity, and also improves the structure and function of endoplasmic reticulum (ER), changes which enhance glucose-stimulated insulin secretion and inhibit the apoptosis of β-cells, leading to β-cell mass preservation. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. Clinical trials into the effects of imeglimin monotherapy and combination therapy exhibited an excellent hypoglycemic efficacy and safety profile in type 2 diabetic patients. Mitochondrial impairment is closely associated with endothelial dysfunction, which is a very early event in atherosclerosis. Imeglimin improved endothelial dysfunction in patients with type 2 diabetes via both glycemic control-dependent and -independent mechanisms. In experimental animals, imeglimin improved cardiac and kidney function via an improvement in mitochondrial and ER function or/and an improvement in endothelial function. Furthermore, imeglimin reduced ischemia-induced brain damage. In addition to glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.https://www.mdpi.com/2079-7737/12/5/726β-cellendoplasmic reticulumglucose-stimulated insulin secretionimegliminmitochondriaendoplasmic reticulum |
| spellingShingle | Hidekatsu Yanai Hiroki Adachi Mariko Hakoshima Hisayuki Katsuyama Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications Biology β-cell endoplasmic reticulum glucose-stimulated insulin secretion imeglimin mitochondria endoplasmic reticulum |
| title | Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications |
| title_full | Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications |
| title_fullStr | Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications |
| title_full_unstemmed | Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications |
| title_short | Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications |
| title_sort | glucose lowering effects of imeglimin and its possible beneficial effects on diabetic complications |
| topic | β-cell endoplasmic reticulum glucose-stimulated insulin secretion imeglimin mitochondria endoplasmic reticulum |
| url | https://www.mdpi.com/2079-7737/12/5/726 |
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