Figures & data
Figure 1. Schematic of β cell mass expansion throughout life. The timeline shows key events and time points in mouse pancreas development and β cell mass expansion under normal circumstances. Underlying the timeline (blue) are the approximate windows of primary and secondary endocrine differentiation. Overlying the timeline (green) are major mechanisms for β cell mass increase at those times: neogenesis early and replication later, although these overlap. The replicative phase is separated into stages (orange): “embryonic” mode and “adult” mode, indicating the switch from dependency on one set of regulatory factors to another around weaning.
Figure 2. Effects of adult β cell CTGF overexpression on β cell function and mass. (A, B) Intraperitoneal glucose tolerance tests reveal no difference in glucose homeostasis between RIP-rtTA control mice (closed squares) and RIP-rtTA;TetO-CTGF mice (open triangles) treated with doxycycline for 1 week (A) or 5 weeks (B) beginning at ~7 weeks of age. (C, D) Immunolabeling of adult pancreata with antibodies against insulin (green) and Ki67 (red) to assess β cell proliferation (blue: DAPI, nuclei) (Magnification 200). (E) There is no difference in the percent of β cell proliferation in CTGF overexpressing mice compared with control mice after one week of doxycycline treatment (p = 0.61). (F) There is no statistically significant difference in β cell mass in CTGF overexpressing mice compared control mice after one week of doxycycline treatment (p = 0.24). In A, n = 8 for control, n = 4 for bigenic. In B, n = 2 for control, n = 2 for bigenic. In E, n = 3 for each genotype. In F, n = 3 for each genotype.
Figure 3. Effects of β cell CTGF overexpression at weaning on β cell function and mass. (A) Intraperitoneal glucose tolerance tests reveal no difference in glucose homeostasis between RIP-rtTA control mice (closed squares) and RIP-rtTA;TetO-CTGF mice (open triangles) treated with doxycycline for one week, beginning at 3 weeks of age. (B, C) Immunolabeling of 4-week-old pancreata with antibodies against insulin (green) and Ki67 (red) to assess β cell proliferation after one week of CTGF overexpression (blue: DAPI, nuclei) (Magnification 200). (D) There is no difference in the percent of β cell proliferation in CTGF overexpressing mice compared with control mice after one week of doxycycline treatment (p = 0.16). (E) β cell mass is unchanged after one week of CTGF overexpression (p = 0.91). In A, n = 8 for control, n = 3 for bigenic. In D, n = 2 for each genotype. In E, n = 2 for each genotype.
Figure 4. Effects of adult β cell CTGF overexpression on islet vascularity. Immunolabeling of control (A, D) and CTGF-overexpressing (B, E) pancreata after one (A, B) or five (D, E) weeks of CTGF induction (insulin: red; PECAM: green; DAPI: blue, nuclei) (Magnification 200). (A-C) Preliminary data suggests that one week of CTGF overexpression may increase islet vascular density in ~7-week-old mice. (D-F) Islet density is not increased after five weeks of CTGF overexpression. In C, n = 1 for each genotype. In F, n = 2 for each genotype.
