4 week old male db/db mice were treated with saline (black line) or TUDCA (150 mg/kg/day; broken line) i.p. for 28 days. (A) The non-fasting blood glucose levels and (B) body weight were monitored 3x/week. (C) HbA1c levels were measured at termination of treatment. (D) ER stress-related gene transcripts were analyzed in islets isolated from saline-treated (open bars) and TUDCA-treated (shaded bars) db/db mice. Fold-change refers to mRNA expression relative to gene expression in wt kidney (broken line) which was assigned a value of 1 and normalized to the house-keeping gene Gapdh. The in situ expression of (E) HSPG core protein (COL18), (F) HS and (G) insulin was determined by immunohistochemistry and evaluated as % islet area stained. (A-B) Data represent mean weekly measurements ± SEM with n = 12–14 male mice/group, n = 3 measurements/mouse; (C) mean ± SEM for n = 12–13 mice/group; (D) mean ± SEM, each data point represents an independent experiment, n = 4 mice/group (100–140 islets/donor); (E-G) n = 4–9 pancreases/group with n = 86–88 (COL18), n = 38–44 (HS) and n = 92–105 (insulin) islets examined/group. *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001, Mann-Whitney test.