Therapeutic potential of cannabinoid receptor 2 in the treatment of diabetes mellitus and its complications.

The biological effects of endocannabinoid system are mediated by two types of receptors, cannabinoid 1 (CB₁) and cannabinoid 2 receptor (CB₂). They play a pivotal role in the management of pain, inflammation, cancer, obesity and diabetes mellitus. CB₂ receptor activity downregulation is hallmark of inflammation and oxidative stress. Strong evidence display the relation between activation of CB₂ receptors with decrease in the pro-inflammatory cytokines and pro-apoptotic factors. Numerous in vitro and in vivo studies have been validated to confirm the role of CB₂ receptor in the management of obesity, hyperlipidemia and diabetes mellitus by regulating glucose and lipid metabolism. Activation of CB₂ receptor has led to reduction of inflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), Nuclear factor kappa beta (NF-κβ) and also amelioration of reactive oxygen species and reactive nitrogen species playing role in apoptosis. Many studies confirmed the role of CB₂ receptors in the insulin secretion via facilitating calcium entry into the pancreatic β-cells. CB₂ receptors also displayed improvement in the neuronal and renal functions by decreasing the oxidative stress and downregulating inflammatory cascade. The present review addresses, potential role of CB₂ receptor activation in management of diabetes and its complications. It also includes the role of CB₂ receptors as an anti-oxidant, anti-apoptotic and anti-inflammatory for the treatment of DM and its complications. Also, an informative summary of CB₂ receptor agonist drugs is provided with their potential role in the reduction of glucose levels, increment in the insulin levels, decrease in the hyperglycaemic oxidative stress and inflammation.