Spontaneous Recovery From Hyperglycemia by Regeneration of Pancreatic [beta]-Cells in Kir6.2G132S Transgenic Mice

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 h...

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Bibliographic Details
Published inDiabetes (New York, N.Y.) Vol. 55; no. 7; p. 1930
Main Authors Oyama, Kazunobu, Minami, Kohtaro, Ishizaki, Katsuhiko, Fuse, Masanori
Format Journal Article
LanguageEnglish
Published New York American Diabetes Association 01.07.2006
Subjects
Cells
Diabetes
Glucagon
Glucose
Hyperglycemia
Hypoglycemia
Insulin
Lectins
Pancreas
Polypeptides
Transgenic animals
Japan
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Summary: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.
ISSN:0012-1797
1939-327X