Basic Research in Diabetic Nephropathy Health Care: A study of the Renoprotective Mechanism of Metformin
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The anti-aging gene klotho is closely related to kidney disease, and an increase in the level of the klotho protein inhibits the progression of various kidney diseases. According to clinical studies, dimethyl-biguanide hydrochloride (DMBG) reduces the urinary protein level in patients with diabetic nephropathy to protect the kidney, but the specific renoprotective mechanism remains unclear. In this study, the application of DMBG partially alleviates the pathological changes in the kidneys of db/db mice, increases the level of the klotho protein in the blood, urine and kidney tissues of the mice, and reduces the levels of the mTOR and p-mTOR proteins. The effects of high glucose and DMBG on klotho and the mTOR pathway in MDCK cells were analyzed at the cellular level. High glucose stimulation activates mTOR pathway and decreases the activity of MDCK cells. DMBG decreases the level of the mTOR protein and reverses the effect of hyperglycaemic stimulation on the activity of MDCK cells. After inhibiting the expression of the klotho protein, DMBG is unable to decrease the level of the mTOR protein. Therefore, klotho plays an important role in the mechanism by which DMBG inhibits the mTOR pathway to protect renal function.
KeywordsDimethyl-biguanide hydrochloride Diabetic nephropathy Klotho mTOR pathway MDCK cells
This study was partially supported by the Youth Foundation of the Commission of Health and Family Planning of Wuxi under grant Q201654.
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Conflict of interest
The authors have no conflicts of interest with the contents of this paper to declare.
This article does not contain any studies with human participants performed by any of the authors.