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

ABSTRACT: Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic ? 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 ? cells. Treatment of MIN6 and ?TC6 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 ? cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of ?-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance ?-cell function and growth in diabetes.

SUBMITTER: Kim J 

PROVIDER: S-EPMC4788443 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Kim Jihye J   Lee Kyung Jin KJ   Kim Jung Seok JS   Rho Jun Gi JG   Shin Jung Jae JJ   Song Woo Keun WK   Lee Eun Kyung EK   Egan Josephine M JM   Kim Wook W  

PloS one 20160311 3

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 inducin  ...[more]

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