Excessive fructose consumption activates the liver protein ChREBP, which drives glucose production independently of insulin signaling, initiating insulin resistance.

Research identifies carbohydrate-responsive element-binding protein (ChREBP) in the liver as a key molecular factor activated by high fructose intake. This activation causes continued glucose production despite insulin presence, leading to elevated blood glucose and insulin levels. This mechanism challenges the traditional view that insulin resistance stems solely from defective insulin receptor signaling.