title: Pancreatic β-cells are generated by neogenesis from non-β-cells after birth.
abstract: The mass of pancreatic β-cells is maintained throughout lifetime to control blood glucose levels. Although the major mechanism of the maintenance of β-cell mass after birth is thought to be selfreplication of pre-existing β-cells, it is possible that pancreatic β-cells are also generated from non-β-cells. Here, we address this issue by using the inducible Cre/loxP system to trace β-cells. We generated Ins2-CreERT2/R26R-YFP double knock-in mice, in which pancreatic β-cells can be labeled specifically and permanently upon injection of the synthetic estrogen analog tamoxifien, and then traced the β-cells by pulse and chase experiment in several different conditions. When β-cells were labeled in adults under physiological and untreated conditions, the frequency of the labeling (labeling index) was not altered significantly throughout the 12-month experimental period. In addition, the labeling index was not changed after ablation of β-cells by streptozotocin treatment. However, when tamoxifen was injected to pregnant mothers just before they gave birth, the labeling index in the neonates was decreased significantly around weaning, suggesting that β-cells are generated from non-β-cells. These results indicate that various mechanisms are involved in the maintenance of β-cells after birth, and that the present system using knock-in mice is useful for investigation of β-cell fate.
authors.affiliation: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Korefumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Minami
authors.forename: Kanako
authors.initials: K
authors.lastname: Tamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Iemoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D005260:Female; D005453:Fluorescence; D015870:Gene Expression / Q000187:drug effects; D005818:Genetic Engineering / Q000379:methods*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D045522:Recombinases / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin / Q000009:adverse effects; D013629:Tamoxifen / Q000008:administration & dosage*; D014886:Weaning
chemical_list: D001426:Bacterial Proteins; D007328:Insulin; D008164:Luminescent Proteins; D045522:Recombinases; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; D013311:Streptozocin; D005947:Glucose