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

Gallo, Linda A., Ward, Micheal S., Fotheringham, Amelia K., Zhuang, Aowen, Borg, Danielle J., Flemming, Nicole B., Harvie, Ben M., Kinneally, Toni L., Yeh, Shang-Ming, McCarthy, Domenica A., Koepsell, Hermann, Vallon, Volker, Pollock, Carol, Panchapakesan, Usha and Forbes, Josephine M. (2016) Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. Scientific Reports, 6 . doi:10.1038/srep26428


Author Gallo, Linda A.
Ward, Micheal S.
Fotheringham, Amelia K.
Zhuang, Aowen
Borg, Danielle J.
Flemming, Nicole B.
Harvie, Ben M.
Kinneally, Toni L.
Yeh, Shang-Ming
McCarthy, Domenica A.
Koepsell, Hermann
Vallon, Volker
Pollock, Carol
Panchapakesan, Usha
Forbes, Josephine M.
Title Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice
Formatted title
Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-05-26
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep26428
Open Access Status DOI
Volume 6
Total pages 17
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
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.
Keyword Blood glucose control
Renin angiotensin system (RAS)
Kidney disease
Diabetes
Empagliflozin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Sun, 19 Jun 2016, 00:24:28 EST by System User on behalf of Learning and Research Services (UQ Library)