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-alpha), Interleukin 6 (IL-6), Nuclear factor kappa beta (NF-kappa beta) 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 beta-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 antioxidant, 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.