Fig. 5: Effect of selective and conditional expression of ∆NIκBα in insulin-producing cells during the embryonic period on glucose tolerance, the degree of insulitis, β-cell mass (BCM), β-cell proliferation, and apoptosis in NOD/ToIβ mice.

A Experimental design: NOD/ToIβ or NOD/LtJ female mice were exposed to Dox during the fetal period until birth (E11–P1). IPGTT was performed at 4 (B), 9 (D), or 14 (F) weeks of age. After an overnight fast, mice were injected with 2 g/kg D-glucose and blood samples were collected at 0, 15, 30, 60, and 120 mins post-loading, and glucose levels were measured. The results are presented as the mean ± SEM of data pooled from untreated controls (black lines, n = 10–16), Dox-treated E11–P1 (red lines, n = 12–13). *P < 0.05 vs control. C, E, G Insulitis scores calculated for 4, 9, and 14 weeks of age: C control, (487 islets, n = 5), E11–P1 (436 islets, n = 5) at 4 weeks; at 9 weeks (E): control (249 islets, n = 4), E11–P1 (457 islets, n = 5); and at 14 weeks (G): control (336 islets, n = 5), E11–P1 (169 islets, n = 6). Values are mean ± SEM. *P < 0.04, **P < 0.009 vs control. H BCM was determined and is presented in milligrams: mice were sacrificed on P1: n = 3; P12: n = 4; 4 weeks: n = 3–5; 9 weeks: n = 3–5 and 14 weeks: n = 3–4): controls (empty bars) or Dox-treated (hatched bars). Values are mean ± SEM. *P < 0.05, **P < 0.01 vs control. I, K, M β-cell proliferation was assessed by co-staining for Ki67, insulin, and calculated as a percent of Ki67-positive nuclei in insulin-positive cells out of the total number of insulin-positive cells per mouse. I P1 (n = 4–5, ~4550 β-cells); K P12 (n = 4, ~7550 β-cells); M 4 weeks (n = 3–4, ~8400 β-cells). J, L, N β-cell apoptosis was assessed using TUNEL assay and co-staining for insulin and calculated as a percent of TUNEL-positive nuclei in insulin-positive cells out of the total number of insulin-positive cells per mouse. J P1 (n = 4–5, ~4600 β-cells); L P12 (n = 4, ~9750 β-cells); N 4 weeks (n = 3–4, ~16,400 β-cells). *P < 0.05.