骨骼肌组织磷脂酰肌醇3-激酶表达与妊娠期糖尿病胰岛素抵抗关系的研究

Relationship between the expression of phosphatidylinositol 3-kinase and insulin resistance in women with gestational diabetes mellitus

目的探讨骨骼肌组织中磷脂酰肌醇3-激酶（phosphatmylinositol 3-kinase，PI-3K）表达与妊娠期糖尿病（gestational diabetes mellitus，GDM）孕妇胰岛素抵抗的关系。方法采用RT—PCR及免疫印迹法测定30例GDM孕妇（GDM组）、30例糖耐量正常孕妇（正常组）及20例糖耐量正常的非孕妇女（对照组）骨骼肌组织PI-3K调节亚单位P85α mRNA及蛋白表达水平。采用葡萄糖氧化酶法及放射免疫法测定空腹葡萄糖（fasting plasma glucose，FPG）、空腹胰岛素（fasting insulin，FINS）水平，计算胰岛素抵抗指数（HOMA—IR）。结果GDM组FPG[（5．61±0．78）mmol／L]、FINS[（15．12±5．31）mU／L]、HOMA—IR（1．21±0．52）分别高于正常组[（4．43±0．46）mmol／L、（10．56±3．07）mU／L和（0．80±0．31），P〈0．01]；正常组FINS、HOMA-IR均明显高于对照组[（7．56±2．31）mU／L和（0．47±0．26），P〈0．01]。GDM组P85α mRNA表达水平（1．08±0．23）明显高于正常组（0．88±0．29）及对照组（0．63±0．26）（P〈0．01）；正常组高于对照组（P〈0．01）。骨骼肌组织中的P85α蛋白表达：GDM组（0．81±0．32）高于正常组（0．55±0．27）和对照组（0．28±0．20）（P〈0．01）；正常组高于对照组（P〈0．01）。P85αmRNA及蛋白表达水平与HOMA—IR在GDM组和正常组呈正相关（r=0．625、0．759，P〈0．01；r=0．514、0．603，P〈0．01），而在对照组无明显相关性（r=0．426、0．395，P〉0．05）。结论骨骼肌组织P85α基因上调导致P85α蛋白表达水平增高，可能是GDM患者发生胰岛素抵抗的分子机制之一。

Objective To investigate the relationship between the expression of phosphatidyli- nositol 3-kinase（PI-3K） in skeletal muscles and insulin resistance in women with gestational diabetes mellitus（GDM）. Methods The expression of PI-3K regulative subunit P85α mRNA and protein in skeletal muscle were determined by RT-PCR and Western blot in pregnant women with GDM （GDM group, n= 30）, normal pregnant women （normal group, n=30） and nonpregnant healthy women （control group, n=20）. Fasting plasma glucose （FPG） and fasting insulin （FINS） were measured by oxidized assay and immunoradioassay. Insulin resistant index （HOMA-IR） was calculated. Results The levels of FPG, FINS, and HOMA-IR in GDM group E（5.61±0.78） mmol/L, （15. 12±5.31） mU/L, and 1.21 ± 0. 52] were significantly higher than those of normal group [（4.43 ± 0. 46） mmol/L, （10.56±3.07） mU/L and 0. 80±0. 31 ; P〈0.01]. The expression of P85α mRNA （1.08±0. 23） and protein （0. 81±0. 32） in GDM group were significantly higher than those in normal group （0.88±0.29 and 0. 55±0. 27, P〈0.01） and control group（0.63±0.26 and 0. 28±0. 20, P〈 0.01）. Expression of P85a mRNA and protein was positively correlated with HOMA-IR （r=0. 625 and 0. 759, P〈0.01） in GDM group, but not in the control group. Conclusions Upregulated P85α mRNA and high expression of P85α protein in skeletal muscle may be one of the molecular mechanisms leading to insulin resisitance in GDM women.