Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells.

ABSTRACT: Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse ?-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating ?-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse ?-cell lines and human islets. In addition, silencing CB1R in mouse ? cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in ? cells lacking insulin receptor. Furthermore, CB1R-/- mice had increased pro-insulin, GCK and GLUT2 expression in ? cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve ?-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to ?-cell function in type 2 diabetes.

SUBMITTER: Shin H 

PROVIDER: S-EPMC5867156 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature