摘要
目的探讨骨骼肌组织中胰岛素受体底物1(IRS-1)表达及其酪氨酸磷酸化与妊娠期糖尿病发生胰岛素抵抗的关系。方法采用蛋白印迹法(western blot)及免疫沉淀法检测22例妊娠期糖尿病患者(妊娠期糖尿病组)、22例正常妊娠妇女(正常妊娠组)及13例正常非孕妇女(正常非孕组)骨骼肌组织中 IRS-1蛋白表达水平及其酪氨酸磷酸化程度;采用放射免疫法及葡萄糖氧化酶法检测各组妇女空腹胰岛素(FINS)及空腹血糖(FPG)水平,并采用稳态模型法计算胰岛素抵抗指数(HOMA-IR)。结果 (1)妊娠期糖尿病组 FPG、FINS、HOMA-IR 分别为(5.6±0.8)mmol/L、(15.4±5.1)mU/L、1.2±0.5,正常妊娠组分别为(4.4±0.5)mmol/L、(10.6±3.1)mU/L、0.8±0.3,两组间各指标分别比较,差异均有统计学意义(P<0.01);正常非孕组 FINS、HOMA-IR 分别为(7.6±2.3)mU/L、0.5±0.3,分别与正常妊娠组比较,差异均有统计学意义(P<0.01)。(2)妊娠期糖尿病组 IRS-1蛋白表达水平为0.64±0.11,明显低于正常妊娠组的0.81±0.13,两组分别比较,差异均有统计学意义(P<0.01);正常非孕组 IRS-1蛋白表达水平为0.83±0.12,与正常妊娠组比较,差异无统计学意义(P>0.05)。(3)妊娠期糖尿病组基础及胰岛素刺激后的 IRS-1酪氨酸磷酸化程度分别为0.35±0.12及0.48±0.14,均低于正常妊娠组的0.38±0.13及0.66±0.12,两组分别比较,差异均有统计学意义(P<0.01);正常妊娠组胰岛素刺激后的 IRS-1酪氨酸磷酸化程度明显低于正常非孕组的0.85±0.09(P<0.01)。(4)妊娠期糖尿病组 IRS-1蛋白表达水平和胰岛素刺激后的酪氨酸磷酸化程度与 HOMA-IR 呈明显负相关(r=-0.613,-0.632;P<0.01);正常妊娠组胰岛素刺激后酪氨酸磷酸化程度与 HOMA-IR 呈明显负相关(r=-0.526,P<0.05)。结论骨骼肌组织中IRS-1蛋白表达及其酪氨酸磷酸化程度异常,是妊娠期糖尿病患者发生胰岛素抵抗的分子机制之一。
Objective To study the relationship between tyrosine phosphorylation（TP） and protein expression of insulin receptor substrate-1 （IRS-1） and insulin resistance in patients with gestational diabetes mellitus （GDM）. Methods IRS-1 expression and TP in skeleton muscle tissue were determined by Western blot and immunoprecipitation in women with GDM （ GDM group, n = 22 ）, normal pregnant women （ normal pregnancy group, n = 22） and normal nonpregnant women（ normal nonpregnant group, n = 13）. Fasting plasma glucose（FPG）and fasting insulin（FINS） were measured by oxidase assay and immunoradioassay. Results （1） The levels of FPG, FINS , and insulin resistance index were calculated according to homeostasis model assessment [ HOMA-IR; （5. 6 ±0. 8 ） mmol/L, （ 15.4 ± 5.1 ） mU/L, and 1.2 ±0. 5 ] in GDM group were significantly higher than those in normal pregnancy group [ （4. 4 ± 0. 5 ） mmol/L, （10. 6 ±3. 1 ） mU/L, and 0. 8 ± 0. 3 ;P 〈 0. 01 ]. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal nonpregnant group [ （7. 6 ±2. 3） mU/L and 0. 5±0. 3;P 〈 0. 01]. （2） The level of IRS-1 protein expression in GDM group （0. 64 ± 0. 11 ）was lower than that in normal pregnancy group（0. 81 ±0. 13 ;P 〈 0. 01 ）. （3） rip with and without insulin stimulation（0. 48±0. 14 ,and 0. 35 ± 0. 12 ） decreased in GDM group, compared with normal pregnancy group （0. 66 ± 0. 12, and 0. 38±0. 13 ;P 〈 0. 01 ）. TP with insulin stimulation in normal pregnancy group was lower than that in normal nonpregnant group（0. 85 ±0. 09 ;P 〈 0. 01 ）. （4） Protein expression and TP with insulin stimulation of IRS- 1 was negatively related to HOMA-IR in GDM group（r = - 0.613, -0.632; P 〈0.01）, and TP with insulin stimulation was negatively related to HOMA-IR in normal pregnancy group （ r = - 0. 526, P 〈 0. 05）. Conclusion Changes in protein expression and tyrosine phosphorylation of IRS-1 in skeletal muscle may be one of the molecular mechanisms leading to insulin resistance in patients with GDM.
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2007年第4期249-252,共4页
Chinese Journal of Obstetrics and Gynecology
关键词
糖尿病
妊娠
胰岛素抗药性
酪氨酸
磷蛋白类
磷酰化
Diabetes, gestational
Insulin resistance
Tyrosine
Phosphoproteins
Phosphorylation
