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J Cell Mol Med. 2018 Apr;22(4):2337-2345. doi: 10.1111/jcmm.13523. Epub 2018 Feb 12.

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

Author information

1
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
2
School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
3
Center for Genomic Integrity, Institute for Basic Science, Ulsan, South Korea.
4
Department of Pharmacology, Ajou University School of Medicine, Suwon, South Korea.
5
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea.
6
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
7
Department of Islet Cell and Regenerative Biology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA, USA.
8
Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Abstract

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

KEYWORDS:

cannabinoid 1 receptor; glucokinase; glucose transporter 2; insulin secretion; β-cell function

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