Effect of Empagliflozin on Tacrolimus‐Induced Pancreas Islet Dysfunction and Renal Injury. Issue 10 (20th May 2017)

• Record Type: Journal Article
• Authors: Jin, J.; Jin, L.; Luo, K.; Lim, S. W.; Chung, B. H.; Yang, C. W.
• Is Part Of: American journal of transplantation. Volume 17:Issue 10(2017)
• Page Start: 2601
• Page End: 2616
• Publication Date: 2017-05-20
• Subjects: basic (laboratory) research/science -- kidney transplantation/nephrology -- diabetes: new onset/posttransplant -- immunosuppressant -- calcineurin inhibitor: tacrolimus; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14316
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : An inhibitor of sodium glucose co‐transporter type 2 (SGLT‐2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus (TAC)‐induced DM. We evaluated the effect of empagliflozin (Em) on TAC‐induced pancreatic islet dysfunction and renal injury in an experimental model of TAC‐induced DM and in vitro . TAC induced a twofold increase in SGLT‐2 expression, while Em decreased SGLT‐2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size, and glucose‐stimulated insulin secretion compared to the TAC group. In kidney, Em alleviated TAC‐induced renal dysfunction and decreased albumin excretion and histological injury compared with the TAC group. Increased oxidative stress and apoptotic cell death by TAC was remarkably decreased with Em in serum and pancreatic and renal tissues. In in vitro study, TAC decreased cell viability and increased reactive oxygen species (ROS) production in both insulin‐secreting beta‐cell derived (INS‐1) and human kidney‐2 (HK‐2) cell lines. Addition of Em increased cell viability and decreased ROS production in HK‐2 but not in INS‐1 cell lines. This suggests that Em is effective in controlling TAC‐induced hyperglycemia and has direct protective effect on TAC‐induced renal injury. Abstract : Empagliflozin, a SGLT2 inhibitor, effectively controls tacrolimus‐induced hyperglycemia and has direct protective effects on tacrolimus‐induced renal injury.