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.
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.
Authors: Jun Shirakawa; Kazuki Tajima; Tomoko Okuyama; Mayu Kyohara; Yu Togashi; Dario F De Jesus; Giorgio Basile; Tatsuya Kin; A M James Shapiro; Rohit N Kulkarni; Yasuo Terauchi Journal: Diabetologia Date: 2020-01-03 Impact factor: 10.122