Short-term sodium-glucose cotransporter 2 inhibition with ipragliflozin enhances engraftment and function in murine...

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose by promoting urinary glucose excretion and also exert anti-inflammatory and organ-protective effects. This study examined the effects of short-term peri-operative SGLT2 inhibition with ipragliflozin on islet transplantation in a mouse model of diabetes. Streptozotocin-induced diabetic mice underwent portal vein islet transplantation and received either ipragliflozin (Tx + Ip, n = 16) or no treatment (Tx, n = 16) during the perioperative period. At 4 weeks after transplantation, outcomes assessed included blood glucose normalization, body weight, glucose tolerance, insulin secretion, and hepatic expression of inflammatory markers and islet-specific genes. The Tx + Ip group showed a higher rate of blood glucose normalization (75% vs. 25%, p < 0.05), improved glucose tolerance, and higher fasting insulin levels compared with the Tx group. Early hepatic expression of inflammatory markers (tumor growth factor-β, interferon-γ, and interleukin-6) was lower in the Tx + Ip group, whereas expression of the islet survival gene Pdx1 was higher on day 5, suggesting enhanced islet engraftment. These findings indicate that short-term perioperative ipragliflozin improves islet transplantation outcomes in diabetic mice by attenuating early inflammation and supporting islet survival and function, with potential translational relevance for clinical islet transplantation strategies.