Witczak C A, Hirshman M F, Jessen N, Fujii N, Seifert M M, Brandauer J, Hotamisligil G S, Goodyear L J
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02215, USA.
Biochem Biophys Res Commun. 2006 Dec 1;350(4):1063-8. doi: 10.1016/j.bbrc.2006.09.158. Epub 2006 Oct 6.
Mice deficient in c-jun-NH(2)-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction-induced muscle [(3)H]2-deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct alterations in muscle. In vivo muscle [(3)H]2-deoxyglucose uptake in response to a glucose injection was also not enhanced by JNK1 deficiency, demonstrating that a circulating factor was not required to observe altered muscle glucose uptake in the knockout mice. JNK1 deficiency did not affect muscle glycogen levels or the protein expression of key molecules involved in glucose metabolism. This study is the first to directly demonstrate that enhanced skeletal muscle glucose metabolism does not underlie the beneficial effects of JNK1 deficiency in lean mice.
缺乏c-jun氨基末端激酶1（JNK1）的小鼠空腹血糖和胰岛素水平降低，并对肥胖诱导的胰岛素抵抗具有保护作用，提示骨骼肌对葡萄糖的处置增加。因此，我们评估了JNK1缺乏是否会增强肌肉葡萄糖代谢。在JNK1基因敲除小鼠中，离体胰岛素或收缩诱导的肌肉[（3）H]2-脱氧葡萄糖摄取未发生改变，表明JNK1不会通过直接改变肌肉来调节血糖水平。JNK1缺乏也未增强体内肌肉对葡萄糖注射的[（3）H]2-脱氧葡萄糖摄取，表明在基因敲除小鼠中观察到的肌肉葡萄糖摄取改变并不需要循环因子。JNK1缺乏不影响肌肉糖原水平或参与葡萄糖代谢的关键分子的蛋白表达。本研究首次直接证明，骨骼肌葡萄糖代谢增强并非JNK1缺乏对瘦小鼠产生有益作用的基础。
