Figure 1.

Relative balance between the offense and defense mechanisms in β‐cell failure. Offense is usually an external stress against the β‐cells, such as an immune‐mediated attack in type 1 diabetes and increased insulin demand due to obesity and insulin resistance in type 2 diabetes. Defense is usually a β‐cell intrinsic mechanism, such as protective mechanisms against oxidative stress, endoplasmic reticulum stress and apoptosis. (a) Normal balance. During a usual offensive attack (yellow arrow), normal defense (blue bar) can protect the β‐cells from failure. (b) Strong offense and defense. During a strong offensive attack, β‐cells can be protected from failure if the defense is sufficiently strong. (c) β‐Cell failure due to strong offense. Faced with a strong offensive attack, β‐cell failure manifests if the defense is not sufficiently strong. (d) β‐Cell failure due to weak defense. Even during a usual or slightly strong offensive attack, β‐cell failure can manifest if the defense is too weak.