Presence of functional cannabinoid receptors in human endocrine pancreas

Abstract

Together, these results suggest a role for endogenous endocannabinoid signalling in regulation of endocrine secretion in the human pancreas.

The Role of the Endocannabinoid System in the Pathogeny of Type 2 Diabetes

“…In this study, the authors did not measure insulin secreted during the glucose tolerance test so it can not be estimated the direct effect on insulin secretion (Doyle, 2011). In another study, they examined glucose tolerance in response to specific CB1 and CB2 receptors agonists and antagonists and they confirmed the specific effect of the CB1 receptor on glucose intolerance with CB2 receptor imparting a degree of glucose tolerance (Bermudez-Silva et al, 2008). Subchronic administration (18 days) of AM251 (6 mg/kg, interperitoneal) decreased circulating plasma glucose and increased glucose tolerance after a glucose load in ob/ob mice (Irwin et al, 2008).…”

“…A possible explanation for all these contrasting results came from a recent publication that proved that many commercial CB1 receptor antibodies exhibit nonspecific interactions (Grimsey et al, 2008). There is evidence for the expression in the pancreatic islet of all the molecules requested for the synthesis and degradation of the endocannabinoids (Bermudez-Silva et al, 2008). In conditions of hyperglycemia, over-expression of biosynthetic endocannabinoid enzymes and low levels of degrading enzymes was noticed.…”

“…In conditions of hyperglycemia, over-expression of biosynthetic endocannabinoid enzymes and low levels of degrading enzymes was noticed. In insulinoma cell lines from rats and also humans islets there were noticed increased levels of the endocannabinoids in response to glucose stimulation (Bermudez-Silva et al, 2008). It is known that -cells are depolarized and they release of calcium in response to glucosestimulated insulin release.…”

Obesity and the Endocannabinoid System: Is There Still a Future for CB1 Antagonists in Obesity?

“…Previous studies have described the presence of both CB 1 and CB 2 receptors in rodent pancreatic β-and non-β-cells [37,82,83]. Similarly, human islets of Langerhans also express cannabinoid receptors as well as the machinery involved in synthesis and degradation of 2-AG [20]. Several lines of evidence suggest that the ECS plays a role in the regulation of insulin secretion.…”

“…In recent years, there has been substantial interest in investigating the role of endocannabinoid signaling in the regulation of metabolism and energy homeostasis, mainly due to the abundance of CB 1 receptor expression in brain regions and peripheral tissues involved in the control of feeding behavior and energy balance. CB 1 receptors, as well as endocannabinoid producing machinery have been described in the gut [17], liver [18], muscle [19•], endocrine pancreas [20] and white adipose tissue [21,22]. In this regard, it is well known that activation of CB 1 receptors promotes appetite and weight gain, while its blockade induces anorexia and weight loss with metabolic effects in mammals [23•].…”