Ipragliflozin L-Proline

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.

Hepatic fibrogenesis represents a significant and escalating global health challenge with few effective treatments. This research explored the anti-fibrotic potential of the sodium-glucose cotransporter 2 (SGLT2) inhibitor Ipragliflozin (IPRA) in a rat model of hepatic fibrogenesis caused by thioacetamide (TAA), with a specific focus on critical pathways of inflammation, fibrosis, and oxidative stress. Groups were designated as follows: a control; a model group receiving TAA (100 mg/kg, twice weekly for 6 weeks); and two therapeutic groups receiving TAA plus either a low (3 mg/kg/day) or high (6 mg/kg/day) oral dose of Ipragliflozin during the final 4 weeks. TAA administration induced severe liver fibrosis, characterized by significant increases in serum ALT, AST, triglycerides, cholesterol, oxidative stress (↓GSH, ↓CAT, ↑MDA), and pro-inflammatory/pro-fibrotic signaling (↑TLR4, ↑IL-1β, ↑NF-κB, ↑TGF-β1). Ipragliflozin treatment, particularly at the 6 mg/kg dose, dose-dependently and significantly attenuated these changes. It restored liver function, normalized the lipid profile, reversed oxidative stress by boosting antioxidant defenses, and suppressed the core inflammatory and profibrotic TLR4/IL-1β/TGF-β1/NF-κB axis. Histopathological and immunohistochemical findings confirmed a reduction in fibrosis and inflammation. These findings highlight Ipragliflozin's promise as a multi-faceted therapeutic agent for liver fibrosis.