Effect of the sodium–glucose cotransporter 2 inhibitor luseogliflozin on pancreatic beta cell mass in db/db mice of different ages

Abstract

To examine the effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on pancreatic beta cell mass in db/db mice of different ages. db/db mice aged 6, 10, 14 and 24 weeks old were fed either standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group). After 4 weeks, immunohistochemistry and gene expression tests were conducted. In 6-week-old db/db mice, immunohistochemistry revealed a significant increase in beta cell mass in the luseo group compared with the control group after 4 weeks of treatment. Gene expression profiling of isolated islets showed upregulation Mafa, Pdx1, Ki67 and Ccnd2 in the luseo group. Beta cell mass decreased with age in db/db mice in the control group. Beta cell mass in the luseo group significantly increased compared with the control group regardless of age, although beta cell mass in the 28-week-old luseo group (4 weeks of treatment in 24-week-old db/db mice) was significantly lower than in the 10-week-old luseo group (4 weeks of treatment in 6-week-old db/db mice). Luseogliflozin preserved beta cell mass in db/db mice. The protective effect was more evident in the earlier phase of diabetes.

Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

“…Recently, Takahashi et al . administered the SGLT2 inhibitor luseogliflozin to 6‐, 10‐, 14‐ and 24‐week‐old db / db mice for 4 weeks, and found that Mafa and Pdx1 expression levels were increased, and the increased proliferation and suppressed apoptosis of pancreatic β‐cells were more evident in mice that were administered the drug earlier.…”

“…We can easily presume that the early start of treatment for diabetes provides organ protection and the duration of treatment definitely influences its effectiveness, so study participants can be divided into two groups whose durations are the same, but were started at different times, namely, "early administration" and "late administration." Recently, Takahashi et al 23 administered the SGLT2 inhibitor luseogliflozin to 6-, 10-, 14-and 24-week-old db/db mice for 4 weeks, and found that Mafa and Pdx1 expression levels were increased, and the increased proliferation and suppressed apoptosis of pancreatic b-cells were more evident in mice that were administered the drug earlier. These results support the present findings and are of great importance, because they showed that SGLT2 inhibitors protect pancreatic b-cells more effectively when administered at the early phase.…”

Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs

“…SGLT2 inhibitors can increase insulin secretion and beta-cell mass but cannot increase insulin sensitivity [ 28 – 30 ]. However, Xu el.…”

Favourable effect of the sodium‐glucose co‐transporter‐2 inhibitor canagliflozin plus the dipeptidyl peptidase‐4 inhibitor teneligliptin in combination on glycaemic fluctuation: An open‐label, prospective, randomized, parallel‐group comparison trial (the CALMER study)

“…One week of treatment with SGLT2 inhibitors in diabetic mice increased expression levels of the glucagon‐like peptide‐1 receptor and key β‐cell factors, which are critical for β‐cell function . Additionally, SGLT2 inhibitor treatment enhanced β‐cell proliferation by reducing oxidative stress in the islet cells . Third, the additive effect could occur via the restoration of liver dysfunction by treatment with SGLT2 inhibitors .…”