Atorvastatin increases autophagic flux and p62/SQSTM1 of kidney cells in hyperglycemic conditions and treatment in combination with insulin improves renal function of streptozotocin (STZ)-induced diabetic rats
Issued Date
2024-01-01
Resource Type
eISSN
25396056
Scopus ID
2-s2.0-85177889084
Journal Title
Journal of Associated Medical Sciences
Volume
57
Issue
1
Start Page
142
End Page
152
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Associated Medical Sciences Vol.57 No.1 (2024) , 142-152
Suggested Citation
Cressey R. Atorvastatin increases autophagic flux and p62/SQSTM1 of kidney cells in hyperglycemic conditions and treatment in combination with insulin improves renal function of streptozotocin (STZ)-induced diabetic rats. Journal of Associated Medical Sciences Vol.57 No.1 (2024) , 142-152. 152. doi:10.12982/JAMS.2024.016 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/91305
Title
Atorvastatin increases autophagic flux and p62/SQSTM1 of kidney cells in hyperglycemic conditions and treatment in combination with insulin improves renal function of streptozotocin (STZ)-induced diabetic rats
Author(s)
Other Contributor(s)
Abstract
Background: Although atorvastatin is commonly used as a hypolipidemic agent, it confers many health benefits in which the underlying mechanisms are not fully understood. We have previously shown that combined treatment of atorvastatin and insulin effectively restored renal function of streptozotocin (STZ)-induced diabetic rats; nevertheless, the underlying mechanism was not known. Objective: To determine whether the reno-protective effect of atorvastatin and insulin is mediated through its impact on autophagy. Materials and methods: Markers of autophagy, LC3, and p62/SQSTM1, in rat kidney tissues and cell lines treated with atorvastatin and/or insulin were determined by Western blot analysis. Results: Levels of both LC3-I and LC3-II proteins in kidney tissues of STZ-diabetic rats treated with atorvastatin and insulin were significantly increased. The autophagic flux was examined in vitro and showed that high glucose culture conditions suppressed the autophagic flux in kidney cells. Treatment with insulin moderately increased the conversion of LC3-I to LC3-II. Interestingly, atorvastatin increased autophagic flux only in the hyperglycemic but not in the normoglycemic condition. p62/SQSTM1 protein level was decreased in response to high glucose treatment but increased with the addition of insulin and/or atorvastatin. Conclusion: This study has demonstrated that atorvastatin may represent a novel regimen in providing prevention and protection for diabetic nephropathy through the underlying mechanisms of inducing autophagy and p62/SQSTM1.