Short-term des-fluoro-sitagliptin treatment (Tx) increases β-cell proliferation. (a) Timing of short-term diabetes therapy (glipizide, exenatide, des-fluoro-sitagliptin, or vehicle [control]), thymidine labeling (BrdU and EdU 1 week each), GTT, and kill (SAC) in 10-week-old B6.129 F1 hybrid mice. (b–e) Islet staining for BrdU (green), insulin (yellow), and EdU (red) in short-term treated mice with (b) vehicle (control), (c) glipizide, (d) exenatide, or (e) des-fluoro-sitagliptin. Scale bar, 100 μm. (f–h) Cumulative β-cell proliferation, measured by thymidine+ (BrdU and EdU) insulin+ cells as percent of total β-cells for the (f) head, (g) tail, and (h) total pancreas. Mean ± standard error of the mean (≥2427 β-cells/pancreas; n = 5 animals/group). *P < 0.05; **P < 0.01; ***P < 0.001.