Background: Recent studies suggest the participation of the endocannabinoid system in the development of type 2 diabetes mellitus, involved with the regulation of physiological and metabolic processes. The endocannabinoid system is expressed in pancreatic islets and presents a key role in gene expression and regulation of pancreatic hormones secretion. In type 2 diabetes patients and in obesity the blood levels of endocannabinoids are increased, however, little is known about the mechanism of actions in islets and its relation with glucose in media.
Methods: Isolated pancreatics islets of mouse were incubated for 24 hours at 5.5mM and 15mM glucose concentration, in the presence of anandamide or THC as cannabinoid receptors agonists, or with antagonist AM251. Glucose-stimulated insulin secretion and intracellular cAMP were analyzed by ELISA and cytosolic calcium changes were measured by spectrofluorometry with FURA-2.
Results: Activation of endocannabioid receptors significantly increases cAMP levels at low glucose concentration, meanwhile no further changes were observed at high-glucose concentration, correlated with a similar effect in insulin secretion. Shor-time exposure to the antagonist decreases insulin secretion under both glucose conditions. Anandamide does not induce changes in intracellular calcium but THC decreases it at high glucose concentration. Antagonist AM251 enhances calcium fluctuations, suggestion an indirect modulation of insulin secretion.
Conclusions: Endocannabinoid receptors modulation regulates intracellular mechanisms involved in insulin secretion, according to glucose exposure, in isolated pancreatic mouse islets.
A. Vilches-Flores: None. G.M. Garcia-Luna: None.