Recovery from diabetes in mice by β cell regeneration
J. Clin. Invest. Tomer Nir, et al. 117:2553 doi:10.1172/JCI32959 [Go to this article.]

Figure 5
SirTac inhibits β cell regeneration. (A) Treatment with SirTac for 14 days immediately after doxycycline withdrawal caused an approximately 80% decrease in β cell proliferation in both wild-type and diabetic mice. Mice were treated with doxycycline from birth to 1 month of age, and sacrificed 2 weeks later. (B) Accumulation of β cells during SirTac treatment, as assessed by administering BrdU to the drinking water between doxycycline withdrawal and sacrifice, concomitant with SirTac administration as in A. Values are mean ± SD (n = 3–6). More than 500 β cells were counted per mouse. *P < 0.05. (C) Representative images of new β cell accumulation in transgenic mice recovering from diabetes in the absence or presence of SirTac. Arrowheads denote BrdU⁺Insulin⁺ cells. (D) Islet morphology at 1 and 3.5 months of age with or without SirTac treatment for months 1–3.5. Note the persistent ablated islet phenotype following SirTac treatment, in contrast to the spontaneous recovery of islet morphology in its absence. Slides were stained for insulin (brown) and hematoxylin (blue). Original magnification, ×350. (E) Abrogation of β cell regeneration in SirTac-treated transgenic mice. Doxycycline was administered from birth to 1 month, after which mice were sacrificed (n = 13) or allowed to recover for 2.5 months in the absence (n = 4) or presence (n = 6) of SirTac. (F) Blood glucose levels of mice treated as in D and E. n = 5 (SirTac-treated wild-type); 4 (untreated transgenic); 9 (SirTac-treated transgenic).