4-PBA, a chemical chaperone, promotes GLP-1R agonist-induced insulin secretion and GLP-1R’s Gq utilization in ER stress-experiencing and db/db islets. (A, B) Islet insulin secretion. Isolated lean mouse islets were sequentially treated with 4-PBA (2.5 mM, 24 hours), tunicamycin (1 μg/ml, 8 hours), and high glucose (Glc, 17 mM, 1 hour) with or without Ex4 (50 nM), YM (200 nM), and MDL (10 μM). (C-E) Islets were isolated from 12-week-old db/db mice and then pretreated with 4-PBA (2.5 mM, 24 hours) before high glucose with indicated reagents. (C) Insulin secretion and (D, E) its fold change. Data are presented as means ± SEM (n = 4). Statistical analyses were performed using either unpaired t-tests (A, D, E) or 1-way ANOVA (B, C). ns, non-significance. *P < .05, **P < .01, ***P < .001.