Phosphorylated S6K1 (Thr389) is a molecular adipose tissue marker of altered glucose tolerance
Phosphorylated S6K1 (Thr389) is a molecular adipose tissue marker of altered glucose tolerance
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DOI：
10.1016/j.jnutbio.2012.01.005
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Manuel Fernandez-Real, Jose
中科院分区：
文献类型：
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作者：
Maria Moreno-Navarrete, Jose;Ortega, Francisco;Manuel Fernandez-Real, Jose
葡萄糖代谢改变的分子组织标记物将成为抗糖尿病药物的潜在靶点。S6K1是胰岛素作用的下游信号。我们旨在评估人类和大鼠脂肪库中（pThr389）S6K1和总S6K1水平作为葡萄糖代谢改变的候选标志物。采用酶联免疫吸附试验（ELISA）测定49例病态肥胖患者脂肪组织样本和18例大鼠笔肾白色脂肪组织样本中（pThr389）S6K1和总S6K1水平。高糖和罗格列酮对人前脂肪细胞的影响已被探讨。2型糖尿病患者皮下脂肪组织中（pThr389）S6K1/（总）S6K1显著升高（0.78 +/- 0.26 vs. 0.55 +/- 0.14， P= 0.02），与SAT空腹血糖（r=0.46， P= 0.04）和糖化血红蛋白（r=0.63， P= 0.02）相关。与空腹血糖（r=0.43）相似。P=.03)和IRS1基因在内脏脂肪组织中表达（r=-0.41， P=.04）。此外，大鼠实验证实，脂肪组织中较高的（pThr389）S6K1/totalS6K1水平与肥胖相关的代谢紊乱有关。（pThr389）S6K1/totalS6K1在大鼠脂肪组织中进行western blot验证。ELISA和western blot数据均显著相关（r=0.85， P= 0.005）。在人前脂肪细胞中，与正常葡萄糖培养基相比，高糖培养基导致（pThr389）S6K1/总S6K1水平升高，罗格列酮组显著降低。总之，在人和大鼠脂肪组织中，磷酸化的S6K1是葡萄糖水平升高的标志。(c) 2013爱思唯尔公司版权所有。
Molecular tissue markers of altered glucose metabolism will be useful as potential targets for antidiabetic drugs. S6K1 is a downstream signal of insulin action. We aimed to evaluate (pThr389)S6K1 and total S6K1 levels in human and rat fat depots as candidate markers of altered glucose metabolism. (pThr389)S6K1 and total S6K1 levels were measured using enzyme linked immune sorbent assay (ELISA) in 49 adipose tissue samples from subjects with morbid obesity and in 18 pen-renal white adipose tissue samples from rats. The effects of high glucose and rosiglitazone have been explored in human preadipocytes. (pThr389)S6K1/(total)S6K1 in subcutaneous adipose tissue was significantly increased subjects with Type 2 diabetes (0.78 +/- 0.26 vs. 0.55 +/- 0.14, P=.02) and associated with fasting glucose (r=0.46, P=.04) and glycated hemoglobin (r=0.63, P=.02) in SAT. Similar associations with fasting glucose (r=0.43. P=.03) and IRS1 (r=-0.41, P=.04) gene expression were found in visceral adipose tissue. In addition, rat experiments confirmed the higher (pThr389)S6K1/totalS6K1 levels in adipose tissue in association with obesity-associated metabolic disturbances. (pThr389)S6K1/totalS6K1 was validated using western blot in rat adipose tissue. Both ELISA and western blot data significantly correlated (r=0.85, P=.005). In human preadipocytes, high glucose medium led to increased (pThr389)S6K1/total S6K1 levels in comparison with normal glucose medium, which was significantly decreased under rosiglitazone administration. In conclusion, in human and rat adipose tissue, phosphorylated S6K1 is a marker for increased glucose levels. (c) 2013 Elsevier Inc. All rights reserved.