Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels.

Salpeter SJ, Klochendler A, Weinberg-Corem N, Porat S, Granot Z, Shapiro AM, Magnuson MA, Eden A, Grimsby J, Glaser B, Dor Y
Endocrinology. 2011 152 (7): 2589-98

PMID: 21521747 · PMCID: PMC3115606 · DOI:10.1210/en.2010-1372

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G(2)-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-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 β-cell replication.

MeSH Terms (21)

Animals Calcium Channel Agonists Calcium Channels Cell Cycle Cell Line Cell Nucleus Cell Proliferation Cyclin D2 Diabetes Mellitus, Experimental Enzyme Inhibitors Gene Expression Regulation Glucose Glycolysis Humans Islets of Langerhans Male Mice Mice, Inbred ICR Mice, Transgenic Organ Culture Techniques RNA, Messenger

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