title: Spontaneous recovery from hyperglycemia by regeneration of pancreatic beta-cells in Kir6.2G132S transgenic mice.
abstract: The ATP-sensitive K(+) channel (K(ATP) channel) in pancreatic beta-cells is a critical regulator in insulin secretion. We previously reported that transgenic mice expressing a dominant-negative form (Kir6.2G132S) of Kir6.2, a subunit of the K(ATP) channel, specifically in beta-cells develop severe hyperglycemia in adults (8 weeks of age). In this study, we conducted a long-term investigation of the phenotype of these transgenic mice. Surprisingly, hyperglycemia was spontaneously improved with concomitant improvement of pancreatic insulin content in the transgenic mice at >25 weeks of age. Insulin-positive cells and pancreatic duodenal homeobox 1 (PDX1)-positive cells both were clearly increased in the older compared with the younger transgenic mice. Interestingly, cells labeled with the lectin Dolichos biflorus agglutinin (DBA), a potential indicator of uncommitted pancreatic epithelial/ductal cells, were detected in the islets of the transgenic mice but not in those of wild-type mice. In addition, a subset of the DBA-labeled cells was positive for PDX1, insulin, glucagon, somatostatin, or pancreatic polypeptide. Moreover, some of the DBA-labeled cells were also positive for a proliferating cell marker. These results show that the Kir6.2G132S transgenic mouse is a useful model for studying beta-cell regeneration and that DBA-labeled cells participate in the process.
authors.affiliation: Division of CellularMolecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. seino@med.kobe-u.ac.jp.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Oyama
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Minami
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ishizaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Fuse
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D005998:Glycine; D006943:Hyperglycemia / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology*; D012694:Serine; D000099161:Kcnj11 Channel
chemical_list: D001786:Blood Glucose; D005998:Glycine; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D012694:Serine; D000099161:Kcnj11 Channel