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 2
Ablation and regeneration of β cells. (A–C) Morphology of islets. Wild-type (A) and transgenic islets in the absence of doxycycline (Figure 1B) showed the typical organization of central β cells and peripheral α cells. Islets from 5-week-old transgenic mice treated with doxycycline for 7 days (i.e., from 4 weeks of age) showed a decrease in the abundance of β cells and a mixed-islet phenotype with multiple non-β cells at the center (B). Twenty-three weeks after the withdrawal of doxycycline (about 28 weeks of age), transgenic islets had a near-perfect architecture (C). Scale bars: 10 μm. (D–F) Morphometric assessment of β cell mass (D), β cell mass normalized to body weight (E), and the fraction of pancreas tissue area covered by β cells (F) in 5- and 28-week-old mice that received doxycycline between weeks 4 and 5 (n = 5–11 per group). Note a significant spontaneous normalization of β cell mass in transgenic mice relative to wild-type littermates undergoing the same treatment. **P < 0.01. (G) Pancreatic insulin content in 5- and 28-week-old mice that received doxycycline between weeks 4 and 5 (n > 3 per group). Values are mean ± SD. (H) Fed blood glucose levels following doxycycline withdrawal in mice treated with doxycycline between 4 and 5 weeks. (I) Glucose tolerance following long-term (>8 months) recovery from diabetes. Some transgenic mice regained not only normal fed and fasting blood glucose levels, but also normal glucose tolerance.