PloS one, 2016-03, Vol.11 (3), p.e0150981-e0150981
2016
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells
- Ist Teil von
- PloS one, 2016-03, Vol.11 (3), p.e0150981-e0150981
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0150981Titel-ID: cdi_plos_journals_1772449886
- Format
- –
- Schlagworte
- Animals, Apoptosis, Apoptosis - genetics, Bcl-2 protein, Biology and Life Sciences, Cannabinoids, Cannabinoids - pharmacology, Caspase, Caspase-3, Cell cycle, Cell Cycle Checkpoints - drug effects, Cell death, Cell growth, Cell Line, Cell Proliferation - genetics, Cell survival, Clonal deletion, Cyclin D2, Cyclin D2 - genetics, Cyclin D2 - metabolism, Cyclin-dependent kinases, Diabetes mellitus, Flow Cytometry, G1 phase, Gene Expression Regulation - drug effects, Glucose, Insulin, Insulin resistance, Insulin-Secreting Cells - drug effects, Insulin-Secreting Cells - metabolism, Kinases, Medicine and Health Sciences, Mice, Mice, Inbred C57BL, Pancreas, Pharmacology, Proto-Oncogene Proteins c-bcl-2 - genetics, Proto-Oncogene Proteins c-bcl-2 - metabolism, Receptor mechanisms, Receptor, Cannabinoid, CB1 - metabolism, Receptor, Cannabinoid, CB1 - physiology, Receptors, Research and Analysis Methods, Rodents, Therapeutic applications