Open AccessBlockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells
Author(s) -
Shin Hanho,
Han Ji Hye,
Yoon Juhwan,
Sim Hyo Jung,
Park Tae Joo,
Yang Siyoung,
Lee Eun Kyung,
Kulkarni Rohit N.,
Egan Josephine M.,
Kim Wook
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13523
Subject(s) - glucokinase , medicine , endocrinology , insulin , glucose homeostasis , pancreatic islets , receptor , glucose transporter , beta cell , biology , insulin oscillation , cannabinoid , cannabinoid receptor , islet , chemistry , insulin resistance , agonist
Cannabinoid 1 receptors ( CB 1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β‐cell lines, human islets and CB 1R‐null ( CB1R −/− ) mice, we have now investigated the role of CB 1Rs in modulating β‐cell function and glucose responsiveness. Synthetic CB 1R 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 CB 1R in mouse β cells resulted in an increased expression of pro‐insulin, glucokinase ( GCK ) and glucose transporter 2 ( GLUT 2), but this increase was lost in β cells lacking insulin receptor. Furthermore, CB1R −/− mice had increased pro‐insulin, GCK and GLUT 2 expression in β cells. Our results suggest that CB 1R 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 CB 1Rs would be beneficial to β‐cell function in type 2 diabetes.