Protective effects of the SGLT2 inhibitor luseogliflozin on pancreatic β‐cells in db/db db/db mice: The earlier and longer, the better

摘要

Aims We compared the protective effects of sodium glucose co‐transporter (SGLT) 2 inhibitor luseogliflozin on pancreatic β‐cells between early and advanced stages of diabetes and between short‐ and long‐term use. Materials and methods Diabetic db/db mice were treated with luseogliflozin for 2 weeks in an early stage of diabetes (7‐9 weeks of age) and an advanced stage of diabetes (16‐18 weeks) for a longer period of time (7‐18 weeks). We performed various morphological analyses of pancreatic islets and examined gene expression profiles in islets after such treatment. Results In diabetic db/db mice, insulin biosynthesis and secretion were markedly increased by luseogliflozin in an early stage of diabetes but not in an advanced stage. In addition, β‐cell mass was preserved by luseogliflozin only in an early stage. Furthermore, when db/db mice were treated with luseogliflozin for a longer period of time, starting from an early stage, β‐cell function and mass were markedly preserved even after a longer period of time compared to untreated db/db mice. Conclusion Luseogliflozin exerts more protective effects in an early stage of diabetes compared to an advanced stage, and longer‐term use of luseogliflozin exerts more beneficial effects on pancreatic β‐cells compared to short‐term use.