Abstract
Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.
Original language | English |
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Article number | 1644 |
Number of pages | 12 |
Journal | Biomedicines |
Volume | 10 |
Issue number | 7 |
DOIs | |
Publication status | Published - 8 Jul 2022 |
Bibliographical note
Funding Information:This research project was funded by the Health Sciences Research Center, King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, through Research Funding Program grant No [G18-00006].
Publisher Copyright:
© 2022 by the authors.
Keywords
- AT1R/ET-1/iNOS axis
- diabetic nephropathy
- kidney fibrosis
- mesangial expansion
- metformin
- renal artery
ASJC Scopus subject areas
- Medicine (miscellaneous)
- General Biochemistry,Genetics and Molecular Biology