Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

Linda A Gallo; Micheal S Ward; Amelia K Fotheringham; Aowen Zhuang; Danielle J Borg; Nicole B Flemming; Ben M Harvie; Toni L Kinneally; Shang-Ming Yeh; Domenica A McCarthy; Hermann Koepsell; Volker Vallon; Carol Pollock; Usha Panchapakesan; Josephine M Forbes

doi:10.1038/srep26428

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Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

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Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

Linda A Gallo, Micheal S Ward, Amelia K Fotheringham, Aowen Zhuang, Danielle J Borg, Nicole B Flemming, Ben M Harvie, Toni L Kinneally, Shang-Ming Yeh, Domenica A McCarthy, …

Scientific Reports, Vol.6, pp.1-17

2016

DOI: https://doi.org/10.1038/srep26428

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Abstract

diabetes complications

nephrons

renal fibrosis

Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

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Title: Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice
Authors: Linda A Gallo (Author) - The University of Queensland
Micheal S Ward (Author) - The University of Queensland
Amelia K Fotheringham (Author) - The University of Queensland
Aowen Zhuang (Author) - The University of Queensland
Danielle J Borg (Author) - The University of Queensland
Nicole B Flemming (Author) - The University of Queensland
Ben M Harvie (Author) - The University of Queensland
Toni L Kinneally (Author) - The University of Queensland
Shang-Ming Yeh (Author) - Queensland University of Technology
Domenica A McCarthy (Author) - The University of Queensland
Hermann Koepsell (Author) - University of Würzburg
Volker Vallon (Author) - University of California, San Diego
Carol Pollock (Author) - The University of Sydney
Usha Panchapakesan (Author) - The University of Sydney
Josephine M Forbes (Author) - The University of Queensland
Publication details: Scientific Reports, Vol.6, pp.1-17
Publisher: Nature Publishing Group
Date published: 2016
DOI: 10.1038/srep26428
ISSN: 2045-2322
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99620506202621
Output Type: Journal article

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Web Of Science research areas: Endocrinology & Metabolism

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