Poles of ATP-sensitive K+ channels in cell survival and differentiation inthe endocrine pancreas

Citation
T. Miki et al., Poles of ATP-sensitive K+ channels in cell survival and differentiation inthe endocrine pancreas, DIABETES, 50, 2001, pp. S48-S51
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
0012-1797 → ACNP
Volume
50
Year of publication
2001
Supplement
1
Pages
S48 - S51
Database
ISI
SICI code
0012-1797(200102)50:<S48:POAKCI>2.0.ZU;2-9
Abstract
To determine the roles of the ATP-sensitive K+ (K-ATP) channels in endocrin e pancreas more directly, two types of genetically engineered Kir6.2 mice m ere developed: mice expressing a dominant-negative form of Kir6.2 specifica lly in beta -cells (Kir6.2G132S Tg mice) and mice lacking Kir6.2 (Kir6.2(-/ -) or Kir6.2 null mice). The Kir6.2G132S Tg mice show severe impairment of K-ATP channel function only in the beta -cells, whereas Kir6.2 null mice ar e completely defective in K-ATP channel function in all of the cells in whi ch Kir6.2 is a constituent of the K-ATP channels, because of the disruption of Kir6.2. Both types of mice show abnormal architecture of the pancreatic islets. The number of beta -cells in Kir6.2G132S Tg mice decreases markedl y with age, whereas that in Kir6.2(-/-) mice decreases slightly. alpha -Cel ls, which are normally present only in the periphery of pancreatic islets, also appear in the center of the islets in both Kir6.2G132S Tg and Kir6.2(- /-) mice. Interestingly, the number of,peptide YY (PW) and glucagon-positiv e cells is markedly increased in Kir6.2 null mice, whereas the number of PP cells and delta -cells is not altered. Apoptotic cells are detected by the TdT-mediated dUTP nick-end labeling (TUNEL) method at a high frequency in both Kir6.2G372S Tg and Kir6.2(-/-) mice compared with the respective contr ols. Thus, studies of Kir6.2G372S Tg and Kir6.2(-/-) mice indicate that K-A TP channels play an important role in cell survival and differentiation in the endocrine pancreas.