The JNK pathway as a therapeutic target for diabetes

Abstract

The hallmark of Type 2 diabetes is insulin resistance and pancreatic β-cell dysfunction. Under diabetic conditions, the c-jun N-terminal kinase (JNK) pathway is activated in various tissues, which is involved in both insulin resistance and β-cell dysfunction. Activation of the JNK pathway interferes with insulin action and reduces insulin biosynthesis, and suppression of the JNK pathway in diabetic mice improves insulin resistance and β-cell function, leading to amelioration of glucose tolerance. Taken together, the JNK pathway is likely to play a central role in the progression of insulin resistance and β-cell dysfunc-tion and, thus, could be a potential therapeutic target for diabe-tes.

Keywords::

• diabetes
• endoplasmic reticulum (ER) stress
• insulin biosynthesis
• insulin resistance
• c-jun N-terminal kinase (JNK) pathway
• oxidative stress