18.97.14.89
18.97.14.89
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PP-F44 : New role of cannabinoid 1 receptor on GLP-1-mediated insulin secretion
( Jihye Kim ) , ( Wook Kim )
UCI I410-ECN-0102-2021-500-000668687
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Objective Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. We have now investigated the role of CB1Rs in modulating incretin-mediated insulin secretion. Methods Using human and mouse islets, several β-cell lines and CB1R-null (CB1R-/-) mice we investigated cannabinoids as regulators of adenylyl cyclase activity and insulin secretion in β cells. We also examined the effect of CB1R on insulin secretion and glucose clearance in vivo by performing an intraperitoneal glucose (1 g/kg body weight) tolerance test in CB1R+/+ and CB1R-/- mice after infusion of the incretin GLP-1 (1.5 pmol/kg·min). Results In pancreatic β-cell lines, synthetic and endogenous CB1R agonists diminished incretin-mediated cAMP accumulation and insulin secretion, and genetic and pharmacological blockade of CB1R resulted in an increase of insulin secretion and improved glucose tolerance in response to a glucose load, when compared to control mice. Furthermore, CB1R-/- mice showed greater glucose-dependent insulin secretion during infusion of GLP-1. Additionally, CB1R-/- mice had increased glucokinase and glucose transporter 2 expression in β cells. Conclusion Our results suggest that CB1R signaling in pancreatic islets may be harnessed to improve β-cell glucose responsiveness and preserve β-cell function in type 2 diabetes. CB1R antagonists contribute to the physiological regulation of glucose homeostasis through inhibiting CB1Rs expressed in peripheral tissues. Now, our findings show that blocking peripheral CB1Rs would be beneficial to β-cell function.

[자료제공 : 네이버학술정보]
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