(A) WT and KIKO mice, 12 to 14 weeks old, were fed regular chow (RD) for 15 weeks and were then randomized to exenatide (Ex) or vehicle (Veh) administration for 12 weeks (n = 7–10 per group). The following assessments were made at the end of the study: (B) Body weight. (C) Glycemia during the insulin tolerance test (ITT). Insulin sensitivity was quantified as area over the curve (AOC) during (D) ITT and (E) homeostatic model assessment of insulin resistance (HOMA-IR). (F) Fasting glycemia (after 16-hour fast). (G) Glycemia, (H) AUC for glucose, and (I) insulin levels during intraperitoneal glucose tolerance test (IPGTT). (J) Insulinogenic index, calculated as incremental insulin divided by incremental glucose (ΔI/ΔG) in the first 15 minutes of the IPGTT. (K) β cell function calculated as insulinogenic index corrected for insulin sensitivity. Ex vivo mouse islet glucose-stimulated insulin secretion (L) and insulin content (M) corrected for total protein (n = 5–6 per group). Data points correspond to individual mice. The median is shown by a horizontal line in the box plots; 25th and 75th percentiles are at the bottom and top of the boxes; and whiskers represent minimum and maximum values. #q < 0.05, KIKO vs. WT; *q < 0.05, **q < 0.01, and ***q < 0.001 Veh vs. Ex; @q < 0.05, and @@q < 0.01 300 mg/dL vs. 30 mg/dL glucose by Kruskal-Wallis test followed by Benjamini, Krieger, and Yekutieli correction for multiple comparisons or by multiple unpaired 2-tailed t tests (1 per time point, panels C, G, and I) followed by Holm-Šídák correction for multiple comparisons.