Fig. 4: Overexpression of circGlis3 protects against β-cell dysfunction and apoptosis in vivo.

a The time pattern of oe-circGlis3-vector injection and HFD feeding (n  =  12 biological animals). b homeostasis model assessment of insulin resistance (HOMA-IR) of the negative control and oe-circGlis3-treated HFD-fed mice (n = 9 biological animals). HOMA-IR was calculated as HOMA-IR = (FBG (mmol/L)×FINS (mIU/L))/22.5. c–e The fasting insulin, proinsulin and proinsulin-to-insulin ratio values in fasting serum levels of the negative control and oe-circGlis3-treated HFD-fed mice (n = 9 biological animals). f, g Intraperitoneal glucose tolerance test (IPGTT) (2 g/kg) and intraperitoneal insulin tolerance test (IPITT) (1 U/kg) were performed in the overnight fasted HFD-fed mice (n = 6 biological animals). The corresponding area under the curve (AUC) was calculated. h in vivo glucose-stimulated insulin secretion (GSIS) were performed in the overnight fasted HFD-fed mice (n = 9 biological animals). The corresponding area under the curve (AUC) was calculated. i, j Insulin secretion in glucose (2.5 mM and 16.7 mM) stimulated islets from mice with HFD-fed for 8 weeks and 16 weeks (n = 6 biological subjects). k β-cell mass in the negative control and oe-circGlis3-treated HFD-fed mice (n = 10 biological animals). l TUNEL assays of pancreatic sections from negative control and oe-circGlis3-treated mice with HFD-fed for 8 weeks and 20 weeks (Red represents positive TUNEL cells, Green represents Insulin; Scale bars represent 100 μm). m Western Blotting showing Pro-Caspase 3, Cleaved-CASPASE 3, BAX, and BCL-2 proteins in islets of the negative control and oe-circGlis3-treated HFD-fed mice. n, o The fasting insulin, proinsulin and proinsulin-to-insulin ratio values in fasting serum levels of the negative control and oe-circGlis3-treated Lepr^db/db mice (n = 6 biological animals). p IPITT (1.5 U/kg) performed in overnight fasted Lepr^db/db mice (n = 6 biological animals). The corresponding area under the curve (AUC) was calculated. q in vivo GSIS (1.5 g/kg body weight) were performed in overnight fasted Lepr^db/db mice (n = 6-9 biological animals). The corresponding area under the curve (AUC) was calculated. r TUNEL assays of pancreatic sections from the negative control and oe-circGlis3-treated Lepr^db/db mice at age from 6 to 12 weeks (Red represents positive TUNEL cells, Green represents Insulin; Scale bars represent 50 μm). s β-cell mass in the negative control and oe-circGlis3-treated Lepr^db/db mice (n = 9 biological animals). b–s For bar and line graphs, data represents mean ± SEM. b–e, k, m–o, s Unpaired two-tailed Student’s t-test. i, j, l, r Two-way ANOVA with Bonferroni’s post-test. f–h, p–q One-way ANOVA with Tukey’s post-test and Unpaired two-tailed Student’s t-test. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.001. Source data are provided as a Source data file.