β-Cell proliferation in Ppx and MLDS-treated PancMet KO mice. A–D: Representative photomicrographs of SH-operated (A and B) and Ppx (C and D) WT (A and C) and PancMet KO (B and D) mouse pancreatic sections obtained at 7 days postsurgery and stained for insulin (green) and Ki67 (red). Arrows indicate Ki67-positive β-cell nuclei. Magnification of the images is ×630. E–G: Quantification of the percentage of Ki67-positive (E), BrdU-positive (F), and pHH3-positive (G) β-cells in SH-operated (n = 3) and Ppx (n = 7) WT and PancMet KO (n = 3 and n = 9, respectively) mice 7 days after surgery. Results are means ± SEM. *P < 0.05 vs. their corresponding SH-operated mice; #P < 0.05 vs. Ppx-WT mice. Values are not significantly different except where indicated. H and I: Representative photomicrographs of MLDS-treated WT (H) and PancMet KO (I) mouse pancreatic sections obtained at 20 days post-MLDS treatment and stained for insulin (green) and BrdU (red). Arrows indicate BrdU-positive β-cell nuclei. Magnification of the images is ×630. J: Quantification of the percentage of BrdU-positive β-cells in untreated (n = 5) and MLDS-treated (n = 10) WT and PancMet KO (n = 5 and n = 5, respectively) mice 20 days after treatment. Results are means ± SEM. *P < 0.05 vs. corresponding untreated mice; #P < 0.05 vs. MLDS-WT mice. Values are not significantly different except where indicated. K: Representative Western blot displaying cyclin D1, D2, cdk-4, and tubulin expression in protein extracts from SH-operated or Ppx PancMet KO and WT islets obtained at 7 days postsurgery. L–N: Densitometric quantitation of cyclin D1 (L), cyclin D2 (M), and cdk-4 (N) in five Western blots performed with five different protein extracts per condition. Results are means ± SEM. *P < 0.05 vs. SH-operated WT or PancMet KO mice; #P < 0.05 vs. Ppx WT mice. Values are not significantly different except where indicated. Ins, insulin.