Research Article Details
| Article ID: | A16781 |
| PMID: | 28180059 |
| Source: | Mol Metab |
| Title: | JNK at the crossroad of obesity, insulin resistance, and cell stress response. |
| Abstract: | BACKGROUND: The cJun-N-terminal-kinase (JNK) plays a central role in the cell stress response, with outcomes ranging from cell death to cell proliferation and survival, depending on the specific context. JNK is also one of the most investigated signal transducers in obesity and insulin resistance, and studies have identified new molecular mechanisms linking obesity and insulin resistance. Emerging evidence indicates that whereas JNK1 and JNK2 isoforms promote the development of obesity and insulin resistance, JNK3 activity protects from excessive adiposity. Furthermore, current evidence indicates that JNK activity within specific cell types may, in specific stages of disease progression, promote cell tolerance to the stress associated with obesity and type-2 diabetes. SCOPE OF REVIEW: This review provides an overview of the current literature on the role of JNK in the progression from obesity to insulin resistance, NAFLD, type-2 diabetes, and diabetes complications. MAJOR CONCLUSION: Whereas current evidence indicates that JNK1/2 inhibition may improve insulin sensitivity in obesity, the role of JNK in the progression from insulin resistance to diabetes, and its complications is largely unresolved. A better understanding of the role of JNK in the stress response to obesity and type-2 diabetes, and the development of isoform-specific inhibitors with specific tissue distribution will be necessary to exploit JNK as possible drug target for the treatment of type-2 diabetes. |
| DOI: | 10.1016/j.molmet.2016.12.001 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |