Figure 3.

Ngn3+ ductal cell contribution to the endocrine cell population is increased during diabetes

(A) Schematic of the AKITA model of diabetes.

(B) Quantification of SST+ or INS+ duct cells per mouse in age-matched (8–12 weeks of age) control (wild type [WT]) or diabetic (AKITA) mice. N = 6 WT and N = 5 AKITA. Diabetic mice exhibited non-fasting blood glucose of 350–500 mg/dL. Data are represented as mean with SD and p values are indicated.

(C) Quantification of ductal cells per mouse in WT or AKITA (diabetic) mice that are INS+/SST−, INS−/SST+, or INS+/SST+. N = 6 WT and N = 5 AKITA. The average of 4 sections per mouse is shown. Data are represented as mean with SD and p values are indicated

(D) Double IF for INS and SST in WT and AKITA. Hormone-expressing ductal cells are shown enlarged (boxed). Scale bars, 25 μm.

(E) Schematic of strategy to label Ngn3-expressing cells in AKITA mice.

(F) Triple IF for INS, SST, and tdTomato. Hormone-expressing cells near the ductal epithelium are shown enlarged (boxed). Scale bars, 50 μm (left) and 10 μm (right).

(G) Quantification of traced SST+ or INS+ duct cells per mouse in age-matched Ngn3-CreERT tamoxifen-injected (N = 3), AKITA; Ngn3-CreERT tamoxifen-injected (N = 3), and Ngn3CreERT non-injected (N = 4) mice. Mice were injected at 8–12 weeks of age and analyzed 1 week after tamoxifen. Data are represented as mean with SD and p values are indicated.

(H) Schematic of the breeding strategy. Akita^+/− mice were crossed to Ngn3^+/− mice.

(I) Non-fasted blood glucose levels in mice of listed genotypes measured at 7 weeks of age. Control Ngn3^+/+, N = 12, AKITA Ngn3^+/+, N = 18; control Ngn3^+/−, N = 5; AKITA Ngn3^+/−, N = 9. Data are represented as mean with SD and p values are indicated.

See also Figure S2.