Fig. 1. β cell–specific Chop deletion reduces insulin in pancreata and in circulation and prevents liver TG accumulation in male DIO mice.

Under normal diet feeding, Chop-floxed (n = 4) and isogenic Chop-deleted (n = 4) littermates were tested 4 months after TAM injections. All mice were male. (A and B) After a glucose injection (1.5 mg/g body weight, intraperitoneally), glucose excursion showed no difference at 30 min after injection (A), whereas serum insulin concentrations were different at 30 min after glucose stimulation (P < 0.05, by Bonferroni’s test after two-way RM-ANOVA) (B). (C) Correlation of the body weight of individual mice with fasting insulin (P < 0.01 by F test, r² = 0.75). (D) Chop-deleted mice cumulative weight gain 4 months after Chop deletion. P = 0.11 by two-tailed Student’s t test. (E) Chop-floxed (n = 3) and congenic control littermates (n = 5, with 4 WT animals and 1 heterozygous animal) were fed with HFD (45% cal from fat) for 20 weeks before tissue harvest. Mice received TAM injections (four times every other day) at 10 weeks of HFD feeding to delete Chop via Cre recombinase. All mice were male. (F) Body weight after Chop deletion (week 20, P < 0.01) (10 weeks after Chop deletion by TAM). (G) Nonfasting blood glucose. (H) Appearance of fresh liver (top) and pancreas organs immediately after tissue dissection for all mice. (I) Liver weight of Chop-deleted animals (Chop βKO, after CreERT-mediated Chop deletion) compared to WT and Het littermate control mice (P = 0.02). (J) Liver TGs in Chop-deleted mice compared to WT and Het littermate control mice (P < 0.05). (K) Pancreatic insulin in Chop-deleted mice compared to littermate control mice (P = 0.11). (L) Liver TG content correlation with pancreatic insulin content on a semi-log plot (P < 0.05). Data plotted are individual mice, with bar and whiskers representing means ± SEM.