@article{e7164f4162ee4f2986c47de53bd6f714,
title = "Differential effects of empagliflozin on microvascular complications in murine models of type 1 and type 2 diabetes",
abstract = "Microvascular complications account for the significant morbidity associated with diabetes. Despite tight glycemic control, disease risk remains especially in type 2 diabetes (T2D) patients and no therapy fully prevents nerve, retinal, or renal damage in type 1 diabetes (T1D) or T2D. Therefore, new antidiabetic drug classes are being evaluated for the treatment of microvascular complications. We investigated the effect of empagliflozin (EMPA), an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), on diabetic neuropathy (DPN), retinopathy (DR), and kidney disease (DKD) in streptozotocin-induced T1D and db/db T2D mouse models. EMPA lowered blood glycemia in T1D and T2D models. However, it did not ameliorate any microvascular complications in the T2D model, which was unexpected, given the protective effect of SGLT2 inhibitors on DKD progression in T2D subjects. Although EMPA did not improve DKD in the T1D model, it had a potential modest effect on DR measures and favorably impacted DPN as well as systemic oxidative stress. These results support the concept that glucose-centric treatments are more effective for DPN in T1D versus T2D. This is the first study that provides an evaluation of EMPA treatment on all microvascular complications in a side-by-side comparison in T1D and T2D models.",
keywords = "Diabetic kidney disease, Diabetic neuropathy, Diabetic retinopathy, Empagliflozin, Oxidative stress",
author = "Eid, {Stephanie A.} and O{\textquoteright}Brien, {Phillipe D.} and Hinder, {Lucy M.} and Hayes, {John M.} and Mendelson, {Faye E.} and Hongyu Zhang and Lixia Zeng and Katharina Kretzler and Samanthi Narayanan and Abcouwer, {Steven F.} and Brosius, {Frank C.} and Subramaniam Pennathur and Savelieff, {Masha G.} and Feldman, {Eva L.}",
note = "Funding Information: This research work used the Cincinnati MMPC for serum lipid profiles measurements (DK059630). Research reported in this publication was also made possible by Core Services supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number U2CDK110768 (Michigan MMPC). Funding was provided by the NIH (1R24082841 to E.L.F., S.F.A., F.C.B., S.P.; R21NS102924 to E.L.F.; P30DK081943 to S.P.; R01EY020582 to S.F.A.; P30EY007003 Kellogg Eye Center Core Center for Vision Research); Novo Nordisk Foundation (NNF14OC0011633 to E.L.F.); Nathan and Rose Milstein Research Fund to S.A.E.; Sinai Medical Staff Foundation Neuroscience Scholar Fund (E.L.F.); NeuroNetwork for Emerging Therapies; the A. Alfred Taubman Medical Research Institute. Funding Information: Funding: This research work used the Cincinnati MMPC for serum lipid profiles measurements (DK059630). Research reported in this publication was also made possible by Core Services supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number U2CDK110768 (Michigan MMPC). Funding was provided by the NIH (1R24082841 to E.L.F., S.F.A., F.C.B., S.P.; R21NS102924 to E.L.F.; P30DK081943 to S.P.; R01EY020582 to S.F.A.; P30EY007003 Kellogg Eye Center Core Center for Vision Research); Novo Nordisk Foundation (NNF14OC0011633 to E.L.F.); Nathan and Rose Milstein Research Fund to S.A.E.; Sinai Medical Staff Foundation Neuroscience Scholar Fund (E.L.F.); NeuroNetwork for Emerging Therapies; the A. Alfred Taubman Medical Research Institute. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = nov,
doi = "10.3390/biology9110347",
language = "English (US)",
volume = "9",
pages = "1--14",
journal = "Biology",
issn = "2079-7737",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",
}