Differential Effects of Empagliflozin on Microvascular Complications in Murine Models of Type 1 and Type 2 Diabetes

Biology

Phillipe D. O’Brien¹  Masha G. Savelieff¹  John M. Hayes¹  Faye E. Mendelson¹  Samanthi Narayanan¹  Eva L. Feldman¹  Stephanie A. Eid¹  Katharina Kretzler¹  Lucy M. Hinder¹  Steven F. Abcouwer²  Subramaniam Pennathur³  Frank C. Brosius³  Hongyu Zhang³  Lixia Zeng³ 

[1] Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA;Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA;Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA;

关键词: diabetic neuropathy;    diabetic retinopathy;    diabetic kidney disease;    empagliflozin;    oxidative stress;   

DOI  :  10.3390/biology9110347

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown