Figure 4.
External stresses and mechanisms in β‐cell failure. (a) Different external stresses and similar final mechanisms of β‐cell failure in different types of diabetes. Different external stresses: immune‐mediated attack in type 1 diabetes, insulin resistance in type 2 diabetes and β‐cell toxic effect (streptozotocin) in other types of diabetes. Different offensive stresses share the same mechanisms, such as oxidative stress, endoplasmic reticulum stress and apoptosis in the final stage of β‐cell failure. (b) Progressive β‐cell failure after diabetes onset. Once the β‐cell mass is reduced, each β‐cell faces increased stress, such as increased insulin demand (overload) and hyperglycemia, leading to the acceleration of β‐cell failure because of oxidative stress and endoplasmic reticulum stress. (c) Sufficient protection against external stresses with a strong defensive mechanism, such as overexpression of thioredoxin, can preserve the functional β‐cell mass in type 1 (NOD mice)50, type 2 (db/db mice)53 and other types of diabetes (single high dose of streptozotocin)50.