Role of JNK in methabolism

Type 2 diabetes is the most serious metabolic disease affecting about 5% of the US population and of growing prevalence worldwide: by the year 2020, 250 million people will be afflicted. Pancreatic β-cell dysfunction and insulin resistance are the hallmark of type 2 diabetes. It has been observed that the signalling pathway of the c-Jun N-terminal Kinases (JNK) is activated in several tissues in diabetic state, and is possibly involved in development of insulin resistance and suppression of insulin biosynthesis.

In fact germ-line ablation of the Jnk1 gene prevents both diet-induced obesity and insulin resistance. Genetic analysis indicates that the effects of JNK1 on insulin resistance can be separated from the effects of JNK1 on obesity. Thus, analysis of mice with tissue-specific defects in Jnk1 gene expression demonstrates that JNK1 in peripheral tissues (e.g. fat, liver, and muscle) influences diet-induced insulin resistance, but not obesity. In contrast, JNK1 in the brain is required for diet-induced obesity. These studies indicate that

JNK1 plays multiple roles in the regulation of insulin resistance, including altered gene expression, hormone/cytokine production, and lipid metabolism.

Together, these studies establish JNK1 as a potential pharmacological target for the development drugs that may be useful for the treatment of insulin resistance, metabolic syndrome, and type 2 diabetes. I will review the recent advances in JNK-linked to obesity associates pathologies and share our observations using mice lacking stress activated Kinsases.