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Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic ß-cells through glycolysis and calcium channels.
Salpeter, Seth J; Klochendler, Agnes; Weinberg-Corem, Noa; Porat, Shay; Granot, Zvi; Shapiro, A M James; Magnuson, Mark A; Eden, Amir; Grimsby, Joseph; Glaser, Benjamin; Dor, Yuval.
Afiliação
  • Salpeter SJ; Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Endocrinology ; 152(7): 2589-98, 2011 Jul.
Article em En | MEDLINE | ID: mdl-21521747
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Cálcio / Ilhotas Pancreáticas / Proliferação de Células / Ciclina D2 / Glucose / Glicólise Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Cálcio / Ilhotas Pancreáticas / Proliferação de Células / Ciclina D2 / Glucose / Glicólise Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2011 Tipo de documento: Article