The Effects of Empagliflozin, an SGLT2 Inhibitor, on Pancreatic β-Cell Mass and Glucose Homeostasis in Type 1 Diabetes

The novel sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has recently been reported to improve glycemic control in streptozotocin-induced type 1 diabetic rats in an insulin-independent manner, via an increase in urinary glucose output. We investigated the potential of empagliflozin to recover Insulin pathways in type 1 diabetes by improving pancreatic β-cell mass. Blood glucose homeostasis was assessed by an intraperitoneal glucose tolerance test. Serum Insulin levels and Insulin mRNA expression were determined using commercial Insulin ELISA kits and real-time quantitative polymerase chain reaction, respectively. Immunohistochemistry was used to investigate β-cell areas, β-cell proliferation, Apoptosis of pancreatic β-cells, and Reactive Oxygen Species production in the pancreatic β-cells. Results showed that glucose tolerance was significantly improved in streptozotocin-induced type 1 diabetic mice treated with empagliflozin. Empagliflozin-treated mice also showed an increase in Insulin mRNA expression. Higher serum Insulin levels were detected in mice treated with empagliflozin compared with the vehicle group. Immunohistochemistry indicated that β-cell area/total pancreatic area and the expression of cell proliferation marker Ki-67 (co-stained with Insulin) were significantly enhanced by empagliflozin treatment. These effects were due, probably, to a reduction in Apoptosis and Reactive Oxygen Species in the pancreatic β-cells. Taken together, the results of this study indicate that empagliflozin may have a beneficial effect on preserving β-cell regeneration, thus improving blood glucose homeostasis in type 1 diabetes mellitus, probably via the protection of pancreatic β-cell from glucotoxicity-induced oxidative stress.