Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic ß-cells through glycolysis and calcium channels.
Endocrinology
; 152(7): 2589-98, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21521747
ABSTRACT
Understanding the molecular triggers of pancreatic ß-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in ß-cell proliferation and mass homeostasis, but its specific function in ß-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent ß-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the ß-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G(2)-M phases of each ß-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent ß-cells and modulates the down-regulation of cyclin D2 in replicating ß-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and ß-cell replication.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Canales de Calcio
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Islotes Pancreáticos
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Proliferación Celular
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Ciclina D2
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Glucosa
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Glucólisis
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Endocrinology
Año:
2011
Tipo del documento:
Article
País de afiliación:
Israel