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.

journal_name

Diabetes

journal_title

Diabetes

authors

Oyama K,Minami K,Ishizaki K,Fuse M,Miki T,Seino S

doi

10.2337/db05-1459

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

1930-8

issue

7

eissn

0012-1797

issn

1939-327X

pii

55/7/1930

journal_volume

55

pub_type

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