The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin. Briefly, cannabis extract, Δ9 -tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells more effectively, relative to rosiglitazone and metformin. The phytocannabinoids had a more pronounced effect in preadipocytes undifferentiated model rather than the differentiated model. They induced a protective effect at the mitochondrial level by preventing overactivity of the succinate dehydrogenase pathway (p < .01), unlike rosiglitazone, through activation of the glycerol-3-phosphate dehydrogenase shuttling system. An increase in oxygen consumption and an increased expression of beta to alpha adrenoceptors (p < .05) in treated cells were noted. These findings contribute toward understanding the mechanism of action of phytocannabinoids in fat cells and highlight the antidiabetic and anti-obesity properties of various phytocannabinoids that could potentially support the treatment of obesity-related insulin resistance.
Keywords: beta/alpha adrenoceptors; glycerol-3-phosphate dehydrogenase shuttling system; insulin-resistance; obesity; phytocannabinoids.
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