Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet beta-cells via CB1 receptors

Regul Pept. 2008 Jan 10;145(1-3):49-53. doi: 10.1016/j.regpep.2007.08.009. Epub 2007 Aug 24.


Obesity is the main risk factor for the development of metabolic syndrome. Endogenous cannabinoids act on the cannabinoid type 1 (CB1) receptor, a GPCR, and stimulate appetite via central and peripheral actions, while blockade of CB1 receptor reduces body weight in humans. In this study, we aimed to explore a role of the peripheral endocannabinoid system in insulin secretion, which could be important in the metabolic effects of the cannabinoid-CB1 system. We found that mRNA for CB1 receptor, but not CB2 receptor, was expressed in mouse pancreatic islets using RT-PCR. Immunohistochemical study revealed that CB1 receptor was expressed in beta-cells. Furthermore, anandamide and a CB1 agonist, arachidonylcyclopropylamide (ACPA), inhibited glucose-induced insulin secretion from mouse pancreatic islets. Both anandamide and ACPA inhibited glucose-induced cytosolic Ca(2+) oscillation in mouse pancreatic beta-cells. These results demonstrate a novel peripheral action of cannabinoids to inhibit insulin secretion via CB1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology
  • Calcium / metabolism*
  • Cannabinoids / pharmacology*
  • Cytosol / metabolism*
  • Endocannabinoids
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Polyunsaturated Alkamides / pharmacology
  • RNA, Messenger / genetics
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*


  • Arachidonic Acids
  • Cannabinoids
  • Endocannabinoids
  • Insulin
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Glucose
  • Calcium
  • anandamide