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Diabetes 55:1930-1938, 2006
DOI: 10.2337/db05-1459
© 2006 by the American Diabetes Association
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Spontaneous Recovery From Hyperglycemia by Regeneration of Pancreatic ß-Cells in Kir6.2G132S Transgenic Mice

Kazunobu Oyama1, Kohtaro Minami2, Katsuhiko Ishizaki1, Masanori Fuse1, Takashi Miki1, and Susumu Seino1,2

1 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
2 Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan

Address correspondence and reprint requests to Susumu Seino, MD, DMSci, Division of CellularMolecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. E-mail: seino{at}med.kobe-u.ac.jp

Abbreviations: ELISA, enzyme-linked immunosorbent assay; KATP channel, ATP-sensitive K+ channel; DBA, Dolichos biflorus agglutinin; PCNA, proliferating cell nuclear antigen; PDX1, pancreatic duodenal homeobox 1; PGP9.5, protein gene product 9.5; PP, pancreatic polypeptide; TUNEL, transferase-mediated dUTP nick-end labeling; OGTT, oral glucose tolerance test

The ATP-sensitive K+ channel (KATP channel) in pancreatic ß-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 KATP channel, specifically in ß-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 ß-cell regeneration and that DBA-labeled cells participate in the process.


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Copyright © 2006 by the American Diabetes Association.