Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway
Abstract
Oxidative stress (OS) and inflammation play essential roles in the development of diabetic nephropathy (DN). Tirzepatide (TZP) has a protective effect in diabetes. However, its underlying mechanism in DN remains unclear. DN model mice were induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg), followed by administration of different doses of TZP (3 and 10 nmol/kg) via intraperitoneal injection for 8 weeks. The effects of TZP on DN were evaluated by detecting DN-related biochemical indicators, kidney histopathology, apoptosis, OS, and inflammation levels. Additionally, to further reveal the potential mechanism, we investigated the role of TZP in modulating the IL-17 pathway. TZP reduced serum creatinine (sCR), blood urea nitrogen (BUN), and advanced glycosylation end products (AGEs) levels, while simultaneously promoting insulin secretion in diabetic mice. Additionally, TZP attenuated tubular and glomerular injury and reduced renal apoptosis levels. Further studies found that TZP increased the levels of SOD and CAT, and decreased MDA. Meanwhile, TZP also reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both mouse serum and kidney homogenates. TZP effectively inhibited the IL-17 pathway, and subsequent intervention with an IL-17 pathway agonist (IL-17A) reversed the suppressive effects of TZP on OS and inflammation. TZP can improve DN by inhibiting OS and inflammation through the suppression of the IL-17 pathway.
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These mechanisms may be less sensitive to the effects of tirzepatide.
“These mechanisms may be less sensitive to the effects of tirzepatide. 28”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [28]
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- Authors
- Yang, Y., Wang, Y., Zhou, Y., Deng, J., & Wu, L.
- Affiliations
- University of Hong Kong - Shenzhen Hospital (CN)
- Ningxia Medical University (CN)
- Southern Medical University Shenzhen Hospital (CN)
- Corresponding author
- Yang, Yong
- ORCID
- Yang, Yong
- Venue
- Molecular and Cellular Biochemistry
- Published
- 2024-07-04
- Volume
- 480
- Issue
- 2
- Pages
- 1241-1254
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- OpenAlex
- W4400312575
- Semantic Scholar
- 4785ccceb2e4ab2b9066fa4ef0d52c9736e6932c
- Cited by
- 35
- References
- 51
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 2
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- tirzepatide, diabetic nephropathy, oxidative stress, inflammation, IL-17 signaling, streptozotocin-induced diabetes, renal apoptosis, inflammatory cytokines, advanced glycation end products, insulin secretion, MDA
- MeSH terms
- Tirzepatide, Animals, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Inflammation, Male, Signal Transduction, Oxidative Stress, Interleukin-17, Mice
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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