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Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes
Abstract
Aim: In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti‐inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. Methods: We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos −/− mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice. Results: We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta‐related fibrosis and NF‐κ Bp65‐mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis. Conclusion: Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy.
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Treatment with saxagliptin (10 mg/kg/day) reduced renal tubulointerstitial inflammation by NF-κBp65-mediated macrophage infiltration in STZ-induced diabetic enos−/− mice.
“Treatment with the DPP-4 inhibitor, saxagliptin (10 mg/kg/day), reduced renal tubulointerstitial inflammation by NF-κBp65-mediated macrophage infiltration in STZ-induced diabetic enos−/− mice [104].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [104]
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References 13 · Cited by 68
Research works printed but not linked: 13
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- 10.1208/s12248-010-9208-y · DOI
- Panchapakesan U, 2013, DPP4 inhibition in human kidney proximal tubular cells ‐ renoprotection in diabetic nephropathy?, J Diabetes Metab, 9, 007
- 10.1124/jpet.111.186866 · DOI
- 10.1016/S0140-6736(98)07019-6 · DOI · Paper page
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Metadata
- Authors
- Gangadharan Komala, M., Gross, S., Zaky, A., Pollock, C., & Panchapakesan, U.
- Affiliations
- Renal Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital University of Sydney St. Leonards NSW Australia
- The University of Sydney (AU)
- Corresponding author
- Panchapakesan, Usha
- Venue
- Nephrology
- Publisher
- Wiley
- Published
- 2016-04-22
- Volume
- 21
- Issue
- 5
- Pages
- 423-431
- ISSN
- 1320-5358 (ISSN-L)
- 1440-1797
- OpenAlex
- W2108320048
- Cited by
- 68
- References
- 13
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 11 · 2020: 11 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 8
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Renal Research Group
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- saxagliptin, DPP-4 inhibitors, diabetic nephropathy, renal protection, tubulointerstitial fibrosis, renal hypertrophy, renal inflammation, macrophage infiltration, NF-κB p65, type 1 diabetes, eNOS knockout mice, streptozotocin-induced diabetes, albuminuria, glomerulosclerosis
- MeSH terms
- Adamantane, Albuminuria, Animals, Blood Glucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Dipeptides, Fibronectins, Fibrosis, Glomerulonephritis, Hypertrophy, Insulin, Kidney, Male, Nephritis, Interstitial, Phosphorylation, Streptozocin, Signal Transduction, Transforming Growth Factor beta, Mice, Knockout, Dipeptidyl Peptidase 4, Smad2 Protein, Smad3 Protein, Transcription Factor RelA, Nitric Oxide Synthase Type III, Dipeptidyl-Peptidase IV Inhibitors
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