Basic Research in Diabetic Nephropathy Health Care: A study of the Renoprotective Mechanism of Metformin

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...

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Published in:Journal of medical systems Vol. 43; no. 8; pp. 266 - 13
Main Authors: Xue, Jing, Wang, Liang, Sun, Zhuxing, Xing, Changying
Format: Journal Article
Language:English
Published: New York Springer US 01.08.2019
Springer Nature B.V
Subjects:
Aging
Animal tissues
Animals
Antidiabetics
Biomedical Research
Diabetes
Diabetes mellitus
Diabetic Nephropathies - drug therapy
Diabetic nephropathy
Distributed Analytics and Deep Learning in Health Care
Glucose
Health care
Health Informatics
Health Sciences
Hypoglycemic Agents - pharmacology
Kidney diseases
Kidneys
Klotho protein
Medicine
Medicine & Public Health
Membrane Proteins - drug effects
Metformin
Metformin - pharmacology
Mice
Nephropathy
Patient Facing Systems
Proteins
Renal function
Statistics for Life Sciences
Stimulation
TOR protein
Urine
mTOR pathway
Diabetic nephropathy
MDCK cells
Klotho
Dimethyl-biguanide hydrochloride
ISSN:0148-5598, 1573-689X, 1573-689X
Online Access:Get full text
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Summary: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.
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ISSN:0148-5598
1573-689X
1573-689X
DOI:10.1007/s10916-019-1412-4