Fig. 7: GRP94 deletion increases β cell susceptibility to HFD-induced β cell death and diabetes progression.
From: GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes
GRP94 KO (n = 12) and Cre control (n = 12) mice fed normal diet (ND) or HFD for 20 weeks. Random-fed blood glucose levels (A), blood glucose levels during an IPGTT (B), and area under the curve (AUC) during an IPGTT after HFD (C). *p < 0.05 versus control-ND, #p < 0.05 versus KO-ND, $p < 0.05 versus control-HFD, one-way ANOVA. D C-peptide secretion during an IPGTT measured before (0 min), 15 min, and 30 min after glucose injection. *p < 0.05 versus control-ND, #p < 0.05 versus KO-ND, $p < 0.05 versus control-HFD, one-way ANOVA. E β cell mass was analyzed in ND-fed and HFD-fed mice. Ten pancreatic sections from each individual mouse (N = 4 per group) were analyzed. *p < 0.05 versus control-ND, #p < 0.05 versus KO-ND, $p < 0.05 versus control-HFD, one-way ANOVA. F Fluorescence analysis from triple staining for TUNEL, insulin, and DAPI. White arrows point to TUNEL+ cells. G Histogram shows percentages of TUNEL-positive β cells in each group. Scale bar, 50 µm. *p < 0.05 versus control-ND, #p < 0.05 versus KO-ND, $p < 0.05 versus control-HFD; one-way ANOVA. H Protein expression in mouse islets isolated from all 4 treatment groups at week 21. Immunoblot shows relative protein expression of GRP94, IGF-1R, p-AKT, AKT, c-Cas-3, and β-actin. *P < 0.05.
