Figure 8: Inhibition of NF-κB activity prevents T1DM progression in SENP1-deficient mice.

(a–g) NF-κB inhibitor rescued the diabetic phenotype. Ten pairs of age-matched Ctrl and SENP1-aP2KO male mice were treated with NF-κB Activation Inhibitor II, JSH-23 or vehicle at 2 mg kg⁻¹ body weight twice a week from the age of 5 weeks for 6 weeks. (a,b) Glucose and insulin levels in Ctrl vehicle, Ctrl JSH-23, SENP1-aP2KO vehicle and SENP1-aP2KO JSH-23 mice at the ages of 5, 7, 9, 11 and 13 weeks were performed. (c) Tissues were collected at the age of week 13. The overall morphology of the pancreases was compared using H&E staining. Representative images of the pancreases from 10 pair mice are shown. Arrowheads indicate structural changes in the islets of SENP1-aP2KO mice with or without JSH-23. (d) Cytokines IL-6, TNF-α, IFN-γ and IL-1β proteins from PATs were measured by ELISArray kits. (e,f) CCL5 level in the islet of Ctrl vehicle, Ctrl JSH-23, SENP1-aP2KO vehicle and SENP1-aP2KO JSH-23 mice at the age of 13 weeks were measured by quantitativePCR with reverse transcription with GAPDH for normalization (e) and immunostaining with anti-CCL5 (f). (g) β-Cell apoptosis. TUNEL in situ cell death staining together with β-cell marker insulin was performed in pancreas. TUNEL-positive β cells are quantified. All results are shown as means±s.e.m., n=10 male mice in each group. The two-tailed Student’s paired t-test was used for the statistical analysis, *P<0.05; **P<0.01; ***P<0.001, compared with Ctrl group; #P<0.05; ##P<0.01; ###P<0.001, compared with KO group with versus without JSH-23. Ctrl, control; NS, non-significance.