Protective effects of metformin on pancreatic β-cell ferroptosis in type 2 diabetes in vivo
Metformin (Met) is the recommended first-line therapeutic drug for type 2 diabetes mellitus (T2DM) and exerts protective effects on β-cell damage. Ferroptosis, a new form of cell death, is associated with pancreatic islet injury in patients with T2DM. However, the protective effects of Met treatment against β-cell damage through ferroptosis modulation remain under-reported. This study investigated the in vivo effects of Met treatment on pancreatic β-cell ferroptosis using two different diabetic mouse models, namely, low-dose streptozotocin (STZ) and high-fat diet (HFD)–induced diabetic mice and db/db mice. Met treatment significantly restored insulin release, reduced cell mortality, and decreased the overproduction of lipid-related reactive oxygen species in the islets of both STZ/HFD-induced diabetic mice and db/db mice. Administration of the Ras-selective lethal 3 injection significantly attenuated the antiferroptosis effects of Met. Mechanistically, Met treatment alleviated β-cell ferroptosis in T2DM, which was associated with the regulation of the GPX4/ACSL4 axis in the islets. In conclusion, our findings highlight the significance of ferroptosis in T2DM β-cell damage and provide novel insights into the protective effects of Met against islet β cells..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:168 |
|---|---|
| Enthalten in: |
Biomedicine & Pharmacotherapy - 168(2023), Seite 115835- |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yue Sun [VerfasserIn] |
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| Links: |
doi.org [kostenfrei] |
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| Themen: |
Ferroptosis |
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| doi: |
10.1016/j.biopha.2023.115835 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
DOAJ095403426 |
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| 520 | |a Metformin (Met) is the recommended first-line therapeutic drug for type 2 diabetes mellitus (T2DM) and exerts protective effects on β-cell damage. Ferroptosis, a new form of cell death, is associated with pancreatic islet injury in patients with T2DM. However, the protective effects of Met treatment against β-cell damage through ferroptosis modulation remain under-reported. This study investigated the in vivo effects of Met treatment on pancreatic β-cell ferroptosis using two different diabetic mouse models, namely, low-dose streptozotocin (STZ) and high-fat diet (HFD)–induced diabetic mice and db/db mice. Met treatment significantly restored insulin release, reduced cell mortality, and decreased the overproduction of lipid-related reactive oxygen species in the islets of both STZ/HFD-induced diabetic mice and db/db mice. Administration of the Ras-selective lethal 3 injection significantly attenuated the antiferroptosis effects of Met. Mechanistically, Met treatment alleviated β-cell ferroptosis in T2DM, which was associated with the regulation of the GPX4/ACSL4 axis in the islets. In conclusion, our findings highlight the significance of ferroptosis in T2DM β-cell damage and provide novel insights into the protective effects of Met against islet β cells. | ||
| 650 | 4 | |a Metformin | |
| 650 | 4 | |a Type 2 diabetes mellitus | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Islets | |
| 653 | 0 | |a Therapeutics. Pharmacology | |
| 700 | 0 | |a Ya-ping Bai |e verfasserin |4 aut | |
| 700 | 0 | |a De-guo Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Yu-jie Xing |e verfasserin |4 aut | |
| 700 | 0 | |a Teng Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a Wen Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Si-min Zhou |e verfasserin |4 aut | |
| 700 | 0 | |a Jin-han Cheng |e verfasserin |4 aut | |
| 700 | 0 | |a Wei-wei Chang |e verfasserin |4 aut | |
| 700 | 0 | |a Xiang Kong |e verfasserin |4 aut | |
| 700 | 0 | |a Xin-ming Yao |e verfasserin |4 aut | |
| 700 | 0 | |a Li-qun Guo |e verfasserin |4 aut | |
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