Department of Biomedical Sciences, University of Padua, 35131, Padua, Italy.
Department of Medicine, University of Padua, Internal Medicine 3, 35128, Padua, Italy.
Sci Rep. 2017 Dec 14;7(1):17569. doi: 10.1038/s41598-017-17809-w.
Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.
胰岛素在葡萄糖代谢中起着重要作用，肥胖和糖尿病患者存在胰岛素信号缺陷。CK2 是一种多功能蛋白激酶，参与基本的细胞途径，在肿瘤中异常升高。在这里，我们报告在人和鼠脂肪细胞中，CK2 抑制通过抵消 Akt 信号和 GLUT4 向质膜的易位来减少胰岛素诱导的葡萄糖摄取。在小鼠中，CK2 在脂肪组织、肝脏和骨骼肌中的胰岛素信号转导中起作用，其急性抑制会损害葡萄糖耐量。值得注意的是，ob/ob 和 db/db 小鼠以及肥胖患者的白色脂肪组织中 CK2 蛋白水平和活性大大上调，无论其胰岛素抵抗的严重程度以及是否存在前驱糖尿病或明显的 2 型糖尿病。通过减肥手术或低热量饮食获得的体重减轻可将 CK2 的过度激活恢复至正常水平。我们的数据表明 CK2 在胰岛素敏感性、葡萄糖稳态和脂肪组织重塑中起核心作用。CK2 的上调被确定为脂肪组织病理性扩张的标志，提示人类肥胖症的一个新的潜在治疗靶点。
