title: Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment.
abstract: Administration 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.
authors.affiliation: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Masateru
authors.initials: M
authors.lastname: Kataoka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawamuro
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shiraki
authors.forename: Rika
authors.initials: R
authors.lastname: Miki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakano
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takanori
authors.initials: T
authors.lastname: Yasukawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kume
authors.forename: Shoen
authors.initials: S
authors.lastname: Kume
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D012038:Regeneration; D013311:Streptozocin / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D001786:Blood Glucose; D013311:Streptozocin