Cellular mechanism of diabetes remission by bariatric surgery

Systemic insulin sensitivity is increased by the energy storage demand of the body and is decreased by a fall in demand.Insulin resistance is a negative feedback response to energy excess in cells.Bariatric surgery removes the energy excess and induces a persistent energy deficit; this underlies the improvement of insulin sensitivity and the remission of type 2 diabetes.The surgery-induced energy deficit is responsible for both weight loss-dependent and weight loss-independent insulin sensitization.The energy deficit corrects mitochondrial overloading in multiple cell types to restore relevant tissue functions, leading to type 2 diabetes remission. Bariatric surgery is a powerful therapy for type 2 diabetes in patients with obesity. The mechanism of insulin sensitization by surgery has been extensively investigated in weight loss-dependent and weight loss-independent conditions. However, a consensus remains to be established regarding the underlying mechanisms. Energy deficit induced by calorie restriction (CR), that occurs both before and after surgery, represents a unique physiological basis for insulin sensitization regardless of weight loss. In support, we integrate evidence in the literature to provide an energy-based view of insulin sensitization as follows: surgery improves insulin sensitivity through the energy deficit induced by CR, leading to correction of mitochondrial overload in multiple cell types; this then triggers functional reprogramming of relevant tissues leading to diabetes remission. Bariatric surgery is a powerful therapy for type 2 diabetes in patients with obesity. The mechanism of insulin sensitization by surgery has been extensively investigated in weight loss-dependent and weight loss-independent conditions. However, a consensus remains to be established regarding the underlying mechanisms. Energy deficit induced by calorie restriction (CR), that occurs both before and after surgery, represents a unique physiological basis for insulin sensitization regardless of weight loss. In support, we integrate evidence in the literature to provide an energy-based view of insulin sensitization as follows: surgery improves insulin sensitivity through the energy deficit induced by CR, leading to correction of mitochondrial overload in multiple cell types; this then triggers functional reprogramming of relevant tissues leading to diabetes remission.