Figure 1.

Role of the ECS in the development of T2DM. Excess food intake and obesity enhance the ECS tone. A hyperactive ECS further contributes to visceral fat accumulation and obesity by reducing energy expenditure and by enhancing both food intake and lipogenesis. Therefore, the ECS is involved in the development of obesity‐dependent insulin resistance. Moreover, an overactive ECS has direct deleterious effects on insulin sensitivity independent of weight gain in peripheral organ of metabolism (liver, adipose tissue, skeletal muscle). Finally, the ECS indirectly contribute to beta cell failure through activation of the Nlrp3‐ASC inflammasome in infiltrating macrophages, resulting in beta cell apoptosis. Both insulin resistance and relative insulin deficiency lead to the development of T2DM.