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Review
. 2012 Feb;180(2):432-42.
doi: 10.1016/j.ajpath.2011.11.003. Epub 2011 Dec 5.

The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications

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Free PMC article
Review

The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications

Béla Horváth et al. Am J Pathol. .
Free PMC article

Abstract

Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions. The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications. This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system. The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.

Figures

Figure 1
Figure 1
Effects of CB1 receptor activation on diabetes and diabetic complications. CB1 receptor activation may indirectly (via its metabolic consequences) or directly enhance diabetes-associated inflammation and ROS generation, promoting tissue injury and the development of diabetic complications. AT rec, angiotensin II receptor type 1; CNS, central nervous system; PMNs, polymorphonuclear leukocytes.
Figure 2
Figure 2
Possible beneficial effects of CB2 receptor activation on diabetes and diabetic complications. CB2 receptor stimulation may exert beneficial effects against various diabetic complications by attenuating high glucose–induced endothelial cell activation and inflammatory response; chemotaxis, transmigration, adhesion, and activation of inflammatory cells; and subsequent proinflammatory responses and ROS generation. PMNs, polymorphonuclear leukocytes; VCAM-1, vascular adhesion molecule-1.

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