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Differential Effects of Empagliflozin on Microvascular Complications in Murine Models of Type 1 and Type 2 Diabetes.
Eid, Stephanie A; O'Brien, Phillipe D; Hinder, Lucy M; Hayes, John M; Mendelson, Faye E; Zhang, Hongyu; Zeng, Lixia; Kretzler, Katharina; Narayanan, Samanthi; Abcouwer, Steven F; Brosius Iii, Frank C; Pennathur, Subramaniam; Savelieff, Masha G; Feldman, Eva L.
Affiliation
  • Eid SA; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • O'Brien PD; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Hinder LM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Hayes JM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Mendelson FE; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Zhang H; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • Zeng L; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kretzler K; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Narayanan S; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Abcouwer SF; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
  • Brosius Iii FC; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • Pennathur S; Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Savelieff MG; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • Feldman EL; Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Biology (Basel) ; 9(11)2020 Oct 22.
Article in En | MEDLINE | ID: mdl-33105667
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.
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Full text: 1 Database: MEDLINE Language: En Year: 2020 Type: Article
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Full text: 1 Database: MEDLINE Language: En Year: 2020 Type: Article