Metformin attenuates diabetic renal injury via the AMPK‑autophagy axis

Sun,Tingli; Liu,Jizhang; Xie,Changying; Yang,Jun; Zhao,Lijie; Yang,Jingbo

doi:10.3892/etm.2021.10010

Metformin attenuates diabetic renal injury via the AMPK‑autophagy axis

Authors:
- Tingli Sun
- Jizhang Liu
- Changying Xie
- Jun Yang
- Lijie Zhao
- Jingbo Yang
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Affiliations: Department of Nephrology, General Hospital of Daqing Oil Field, Daqing, Heilongjiang 163001, P.R. China, Department of Geriatrics, General Hospital of Daqing Oil Field, Daqing, Heilongjiang 163001, P.R. China
Published online on: March 31, 2021 https://doi.org/10.3892/etm.2021.10010
Article Number: 578
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) is a clinical condition characterized by kidney damage that is observed in patients with diabetes. DN is the main cause of end‑stage renal disease (ESRD), which is the final stage of chronic kidney disease. Increasing evidence suggests that metformin, a characteristic oral hypoglycemic drug used for treating diabetes, exerts beneficial effects on various medical conditions and diseases, including cancer, cardiovascular diseases and thyroid‑related disorders. However, the impact of metformin on DN remains unknown. The present study investigated whether metformin could attenuate the inflammatory response, fibrosis and increased oxidative stress observed during DN in diabetic/dyslipidemic (db/db) mice. The kidneys of the mice (12‑16 weeks) were isolated for immunohistochemistry and western blotting. The results demonstrated that metformin significantly reduced the oxidative damage and fibrosis in the kidneys of db/db mice. Furthermore, metformin treatment significantly inhibited the generation of inflammatory cytokines, including TNF‑α and IL‑1β in db/db mice. These effects were induced by the activation of the AMP‑activated protein kinase (AMPK) pathway, which was mediated by increased phosphorylation of AMPK and mammalian target of rapamycin (mTOR), resulting in autophagy and the simultaneous decrease in reactive oxygen species production, cell apoptosis and inflammatory response. These findings suggested that metformin may reduce DN damage via regulation of the AMPK‑mTOR‑autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN.

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