Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
Trends Biochem Sci. 2010 Sep;35(9):490-6. doi: 10.1016/j.tibs.2010.04.004. Epub 2010 May 7.
The cJun NH(2)-terminal kinase isoform JNK1 is implicated in the mechanism of obesity-induced insulin resistance. Feeding a high-fat diet causes activation of the JNK1 signaling pathway, insulin resistance, and obesity in mice. Germ-line ablation of Jnk1 prevents both diet-induced obesity and insulin resistance. Genetic analysis indicates that the effects of JNK1 on insulin resistance can be separated from effects of JNK1 on obesity. Emerging research indicates 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 of drugs that might be useful for the treatment of insulin resistance, metabolic syndrome, and type 2 diabetes.
cJun N 末端激酶同工酶 JNK1 参与肥胖引起的胰岛素抵抗的机制。高脂饮食可导致 JNK1 信号通路的激活、胰岛素抵抗和肥胖。Jnk1 的种系缺失可预防饮食诱导的肥胖和胰岛素抵抗。遗传分析表明,JNK1 对胰岛素抵抗的影响可与 JNK1 对肥胖的影响分开。新的研究表明,JNK1 在胰岛素抵抗的调节中发挥多种作用,包括改变基因表达、激素/细胞因子的产生和脂质代谢。这些研究共同确立了 JNK1 作为开发可能对治疗胰岛素抵抗、代谢综合征和 2 型糖尿病有用的药物的潜在药理学靶点。