title: Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
abstract: 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.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
authors.forename: Jun Gi
authors.initials: JG
authors.lastname: Rho
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Shin
authors.affiliation: Department of Life Science, Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, 61005, South Korea.
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, United States of America.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
authors.forename: Wook
authors.initials: W
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002186:Cannabinoids / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D056742:Cyclin D2 / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D002186:Cannabinoids; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D019253:Proto-Oncogene Proteins c-bcl-2; D043884:Receptor, Cannabinoid, CB1