Rea R, Donnelly R
Centre for Integrated Systems Biology and Medicine, School of Medical and Surgical Sciences, University of Nottingham, UK.
Diabetes Obes Metab. 2006 Jan;8(1):105-9. doi: 10.1111/j.1463-1326.2005.00477.x.
The adipocyte-secreted hormone resistin has been implicated in obesity-induced insulin resistance and type 2 diabetes, but pharmacological and dietary factors that regulate resistin gene expression and the effects of resistin on cellular glucose uptake in muscle have not been clearly defined.
Expression of resistin mRNA was studied in differentiated 3T3-L1 adipocytes by using real-time semiquantitative reverse transcription-polymerase chain reaction. The effects of resistin on insulin-stimulated and insulin-independent 2-deoxyglucose uptake were evaluated in L6 muscle cells.
Insulin 1 microm and rosiglitazone 10 microm markedly reduced resistin mRNA expression (relative to the control gene TF2D) by 4.7-fold (p < 0.05) and 5.3-fold (p < 0.02), respectively. Similar reductions in resistin mRNA were demonstrated with metformin 100 microm (6.2-fold reduction, p < 0.02) and oleic acid 100 microm (3.9-fold reduction, p < 0.03). Resistin 1 microm significantly reduced maximum insulin-stimulated 2-deoxyglucose uptake in L6 cells from 634 to 383% (relative to 100% for control, p < 0.001), and co-administration of rosiglitazone had no effect on resistin-induced insulin resistance. In the absence of insulin, however, resistin increased glucose uptake dose-dependently (e.g., 1.75-fold at 5 microm, p < 0.001) via a mitogen-activated protein kinase-dependent pathway.
These results demonstrate that various glucose-lowering therapies and oleic acid reduce resistin gene expression in isolated adipocytes, and that resistin impairs insulin-stimulated glucose uptake in skeletal muscle-derived cells.
脂肪细胞分泌的抵抗素与肥胖诱导的胰岛素抵抗及2型糖尿病有关，但调节抵抗素基因表达的药理和饮食因素以及抵抗素对肌肉细胞葡萄糖摄取的影响尚未明确界定。
采用实时半定量逆转录-聚合酶链反应研究分化的3T3-L1脂肪细胞中抵抗素mRNA的表达。在L6肌肉细胞中评估抵抗素对胰岛素刺激和非胰岛素依赖的2-脱氧葡萄糖摄取的影响。
1微摩尔胰岛素和10微摩尔罗格列酮分别使抵抗素mRNA表达（相对于对照基因TF2D）显著降低4.7倍（p<0.05）和5.3倍（p<0.02）。100微摩尔二甲双胍（降低6.2倍，p<0.02）和100微摩尔油酸（降低3.9倍，p<0.03）也使抵抗素mRNA有类似程度的降低。1微摩尔抵抗素使L6细胞中最大胰岛素刺激的2-脱氧葡萄糖摄取从634%显著降低至383%（相对于对照的100%，p<0.001），同时给予罗格列酮对抵抗素诱导的胰岛素抵抗无影响。然而，在无胰岛素的情况下，抵抗素通过丝裂原活化蛋白激酶依赖性途径剂量依赖性地增加葡萄糖摄取（例如，5微摩尔时增加1.75倍，p<0.001）。
这些结果表明，各种降糖疗法和油酸可降低分离脂肪细胞中的抵抗素基因表达，且抵抗素会损害骨骼肌来源细胞中胰岛素刺激的葡萄糖摄取。
