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The endocannabinoid system (ECS) regulates cellular homeostasis and whole-body metabolism. There is an autonomous ECS in the endocrine pancreas, including the cannabinoid 1 receptor (CB1R) that is present in β-cells. Here, we discuss conflicts that have arisen with regard to the function(s) of the ECs in the endocrine pancreas and that have caused confusion when defining the role of the ECS in islets of Langerhans, especially the role(s) of CB1R in β-cells. We also discuss the latest data published concerning the ECS in islets. CB1R in particular is not simply a negative modulator of insulin secretion as it is also involved in intra-islet inflammation during high fat-high sugar intake and it is a negative regulator of β-cell viability and turnover. We also discuss the feasibility of using CB1R as a target for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

The mechanisms regulating incretin secretion are not fully known. Human obesity is associated with altered incretin secretion and elevated endocannabinoid levels. Since cannabinoid receptors (CBRs) are expressed on incretin-secreting cells in rodents, we hypothesized that endocannabinoids are involved in the regulation of incretin secretion. We compared plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) responses during oral glucose tolerance test (OGTT) in 20 lean and 20 obese participants from the Baltimore Longitudinal Study of Aging (BLSA). Next, we recruited 20 healthy men to evaluate GIP and GLP-1 responses during OGTT after administering placebo or nabilone (CBR agonist) in a randomized, double-blind, crossover fashion. Compared with the BLSA lean group, the BLSA obese group had significantly higher fasting and post-OGTT GIP levels, but similar fasting GLP-1 and significantly lower post-OGTT GLP-1 levels. In the nabilone vs. placebo study, when compared with placebo, nabilone resulted in significantly elevated post-dose fasting GIP levels and post-OGTT GIP levels, but no change in post-dose fasting GLP-1 levels together with significantly lower post-OGTT GLP-1 levels. Glucose levels were not different with both interventions. We conclude that elevated GIP levels in obesity are likely a consequence of increased endocannabinoid levels. CBRs exert tonic control over GIP secretion, which may have a homeostatic effect in suppressing GLP-1 secretion. This raises the possibility that gut hormones are influenced by endocannabinoids. [ABSTRACT FROM AUTHOR]