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A comprehensive review explores the endocannabinoid system’s impact on pancreatic islet physiology and dysfunction and its potential as a treatment target for metabolic syndrome, obesity, and diabetes.

  • The endocannabinoid system plays a vital role in metabolism regulation and other physiological processes.
  • The endocannabinoid system is active within the pancreatic islets, impacting insulin and glucagon expression and secretion.
  • Research shows that over-stimulation of the endocannabinoid system in pancreatic islets can lead to glucose intolerance.
  • Contradictory results in studies using different endocannabinoid system agonists and antagonists highlight its complex interaction in pancreatic islet function.

The endocannabinoid system (ECS), first discovered through the therapeutic use of cannabis, is a lipid-signaling complex implicated in regulating metabolism and specific physiological processes. As this review, published in the journal Islets, demonstrates, this complex system has been identified in various organs and tissues, including the pancreatic islets. Its activity in the islets is linked to insulin and glucagon expression, secretion, and stimulation, and in the development of diabetes and other metabolic disorders.

Pancreatic Islet Response to Endogenous and Synthetic Cannabinoid Receptor Agonists

Studies with both endogenous and synthetic cannabinoid receptor agonists have shown diverse responses in the pancreatic islets. Some experiments demonstrated a reduction in glucose-induced insulin secretion, while others reported increased basal and glucose-stimulated insulin secretion. These contradictory results suggest a complex and nuanced physiological interaction within the ECS. Additionally, research shows an increase in endocannabinoid production in islets in obese and diabetic models, likely leading to over-activation of the ECS and consequent metabolic disruptions involved in insulin secretion.

The Potential of Cannabinoid Receptor Antagonists in Treating Metabolic Disorders

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Research into the use of cannabinoid receptor antagonists has yielded promising results for the potential treatment of metabolic disorders. One compound, rimonabant, showed significant reduction in adipose mass in obese and diabetic patients in clinical trials. Furthermore, it was shown to improve carbohydrate and lipid metabolisms in peripheral tissues. Such treatments could help delay islet cell dysfunction, reduce obesity, and improve insulin sensitivity, offering a promising future direction in metabolic disorder management.

Potential Therapeutic Avenues 

This comprehensive review of the ECS and its role in pancreatic islet function offers valuable insights for healthcare providers treating metabolic disorders such as diabetes and obesity. As the ECS shows potential for therapeutic intervention, clinicians need to stay abreast of research developments in this area. These findings may also prompt a reevaluation of treatment strategies, incorporating new therapeutic approaches aimed at modulating the ECS. More research is needed to fully understand the intricate mechanisms of the ECS within the pancreatic islets and the potential therapeutic benefits of manipulating this system.


Cortes-Justo, E., Garfias-Ramírez, S. H., & Vilches-Flores, A. (2023). The function of the endocannabinoid system in the pancreatic islet and its implications on metabolic syndrome and diabetes. Islets, 15(1), 1–11. https://doi.org/10.1080/19382014.2022.2163826