Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

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 c...

Full description

Saved in:
Bibliographic Details
Main Authors: Jihye Kim, Kyung Jin Lee, Jung Seok Kim, Jun Gi Rho, Jung Jae Shin, Woo Keun Song, Eun Kyung Lee, Josephine M Egan, Wook Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150981&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850188870780452864
author Jihye Kim
Kyung Jin Lee
Jung Seok Kim
Jun Gi Rho
Jung Jae Shin
Woo Keun Song
Eun Kyung Lee
Josephine M Egan
Wook Kim
author_facet Jihye Kim
Kyung Jin Lee
Jung Seok Kim
Jun Gi Rho
Jung Jae Shin
Woo Keun Song
Eun Kyung Lee
Josephine M Egan
Wook Kim
author_sort Jihye Kim
collection DOAJ
description 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.
format Article
id doaj-art-3d072aa5f075401ba5fd414dc54bf3cb
institution OA Journals
issn 1932-6203
language English
publishDate 2016-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-3d072aa5f075401ba5fd414dc54bf3cb2025-08-20T02:15:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015098110.1371/journal.pone.0150981Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.Jihye KimKyung Jin LeeJung Seok KimJun Gi RhoJung Jae ShinWoo Keun SongEun Kyung LeeJosephine M EganWook KimRecent 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150981&type=printable
spellingShingle Jihye Kim
Kyung Jin Lee
Jung Seok Kim
Jun Gi Rho
Jung Jae Shin
Woo Keun Song
Eun Kyung Lee
Josephine M Egan
Wook Kim
Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
PLoS ONE
title Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
title_full Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
title_fullStr Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
title_full_unstemmed Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
title_short Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.
title_sort cannabinoids regulate bcl 2 and cyclin d2 expression in pancreatic β cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150981&type=printable
work_keys_str_mv AT jihyekim cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT kyungjinlee cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT jungseokkim cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT jungirho cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT jungjaeshin cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT wookeunsong cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT eunkyunglee cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT josephinemegan cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells
AT wookkim cannabinoidsregulatebcl2andcyclind2expressioninpancreaticbcells