Roles of ATP-sensitive K+ channels in cell survival and differentiation in the endocrine pancreas.
To determine the roles of the ATP-sensitive K+ (K(ATP)) channels in endocrine pancreas more directly, two types of genetically engineered Kir6.2 mice were developed: mice expressing a dominant-negative form of Kir6.2 specifically 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 are completely defective in K(ATP) channel function in all of the cells in which 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 markedly with age, whereas that in Kir6.2-/- mice decreases slightly. alpha-Cells, 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 (PYY) and glucagon-positive 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 controls. Thus, studies of Kir6.2G372S Tg and Kir6.2-/- mice indicate that K(ATP) channels play an important role in cell survival and differentiation in the endocrine pancreas.
Department of Molecular Medicine, Chiba University Graduate School of Medicine, Japan.
T
T
Miki
T
T
Iwanaga
K
K
Nagashima
Y
Y
Ihara
S
S
Seino
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D005838:Genotype; D007515:Islets of Langerhans / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate