Premium
Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes
Author(s) -
Gangadharan Komala Muralikrishna,
Gross Simon,
Zaky Amgad,
Pollock Carol,
Panchapakesan Usha
Publication year - 2016
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12618
Subject(s) - medicine , saxagliptin , diabetic nephropathy , fibrosis , endocrinology , albuminuria , diabetes mellitus , pioglitazone , glomerulosclerosis , dipeptidyl peptidase 4 , dipeptidyl peptidase 4 inhibitor , type 2 diabetes , streptozotocin , inflammation , linagliptin , nephropathy , kidney , sitagliptin , proteinuria
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.