• Masateru Kataoka, Yuki Kawamuro, Nobuaki Shiraki, Rika Miki, Daisuke Sakano, Tetsu Yoshida, Takanori Yasukawa, Kazuhiko Kume, and Shoen Kume.
• Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811, Japan.
• Biochem. Biophys. Res. Commun. 2013 Jan 18; 430 (3): 1103-8.

AbstractAdministration of streptozotocin (STZ) induces destruction of β-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of β-cells, β-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, β-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in β-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of β-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of β-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35-50. This was followed by a spontaneous regeneration of β-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the β-cell mass revealed that the β-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the β-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, β-cell duplication is one of the cell sources for β-cell regeneration.Copyright © 2012 Elsevier Inc. All rights reserved.

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