Shao J, Catalano P M, Yamashita H, Ishizuka T, Friedman J E
Department of Nutrition, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, USA.
Am J Obstet Gynecol. 2000 Nov;183(5):1263-70. doi: 10.1067/mob.2000.106816.
We compared the insulin-mimetic effects of vanadate, a protein-tyrosine phosphatase inhibitor, with the effects of insulin on skeletal muscle glucose transport and insulin receptor and insulin receptor substrate 1 phosphorylation to test the hypothesis that protein-tyrosine phosphatases participate in pregnancy-induced insulin resistance.
Skeletal muscle fiber strips were obtained from the rectus abdominis during cesarean delivery in 7 patients with gestational diabetes mellitus, 11 pregnant women with normal glucose tolerance (pregnant control group), and 11 nonpregnant women undergoing elective surgery (nonpregnant control group). Muscle tissues were incubated in vitro for 15 to 60 minutes with or without maximal insulin (100 nmol/L) or sodium vanadate (6 micromol/L). Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation were measured, as was 2-deoxyglucose transport. The levels of protein-tyrosine phosphatase 1B were measured by Western blot analysis.
Vanadate stimulated maximal 2-deoxyglucose transport more than did insulin alone in all samples (P<.05), but the value was still less in muscle tissues from pregnant control subjects and patients with gestational diabetes mellitus (P<.05). In muscle tissues from pregnant control subjects vanadate increased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 to levels similar to those in muscle tissues from nonpregnant control subjects. In patients with gestational diabetes mellitus vanadate increased insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation, but these values remained less than in muscle tissues from nonpregnant control subjects (P<.05). Protein-tyrosine phosphatase 1B levels were not significantly different in skeletal muscles from each group.
Vanadate did not restore normal glucose transport activity during pregnancy complicated by gestational diabetes mellitus, which indicates that decreased glucose uptake is probably not caused by impaired tyrosine phosphorylation events alone. Increased serine kinase activity and impaired glucose transporter 4 translocation probably contribute to insulin signaling abnormalities associated with pregnancy, especially in patients with gestational diabetes mellitus.
我们比较了蛋白酪氨酸磷酸酶抑制剂钒酸盐的胰岛素模拟作用与胰岛素对骨骼肌葡萄糖转运、胰岛素受体及胰岛素受体底物1磷酸化的作用，以检验蛋白酪氨酸磷酸酶参与妊娠诱导的胰岛素抵抗这一假说。
在剖宫产手术中，从7例妊娠期糖尿病患者、11例糖耐量正常的孕妇（妊娠对照组）和11例接受择期手术的非孕妇（非妊娠对照组）的腹直肌获取骨骼肌纤维条。将肌肉组织在体外孵育15至60分钟，分别加入或不加入最大剂量胰岛素（100 nmol/L）或钒酸钠（6 μmol/L）。检测胰岛素受体及胰岛素受体底物1的酪氨酸磷酸化水平以及2-脱氧葡萄糖转运情况。通过蛋白质印迹分析测定蛋白酪氨酸磷酸酶1B的水平。
在所有样本中，钒酸盐刺激最大2-脱氧葡萄糖转运的作用比单独使用胰岛素更强（P<0.05），但妊娠对照组和妊娠期糖尿病患者肌肉组织中的该值仍较低（P<0.05）。在妊娠对照组的肌肉组织中，钒酸盐使胰岛素受体及胰岛素受体底物1的酪氨酸磷酸化水平升高至与非妊娠对照组肌肉组织相似的水平。在妊娠期糖尿病患者中，钒酸盐增加了胰岛素受体及胰岛素受体底物1的酪氨酸磷酸化，但这些值仍低于非妊娠对照组的肌肉组织（P<0.05）。各组骨骼肌中蛋白酪氨酸磷酸酶1B的水平无显著差异。
在合并妊娠期糖尿病的妊娠期间，钒酸盐未能恢复正常的葡萄糖转运活性，这表明葡萄糖摄取减少可能并非仅由酪氨酸磷酸化事件受损所致。丝氨酸激酶活性增加及葡萄糖转运蛋白4易位受损可能导致与妊娠相关的胰岛素信号异常，尤其是在妊娠期糖尿病患者中。
