Downregulated IRS-1 and PPARγ in obese women with gestational diabetes:: relationship to FFA during pregnancy
Downregulated IRS-1 and PPARγ in obese women with gestational diabetes:: relationship to FFA during pregnancy
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DOI：
10.1152/ajpendo.00124.2001
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发表时间：
2002-03-01
影响因子：
5.1
通讯作者：
Friedman, JE
中科院分区：
文献类型：
--
作者：
Catalano, PM;Nizielski, SE;Friedman, JE
妊娠期糖尿病（GDM）与餐后游离脂肪酸（FFA）升高和胰岛素抵抗有关;然而，对妊娠期胰岛素抵抗抑制脂解的细胞机制知之甚少。我们评估了糖耐量正常的肥胖受试者和肥胖GDM受试者在妊娠前、妊娠早期（12-14周）和妊娠晚期（34-36周）FFA胰岛素抑制的纵向变化。腹部皮下脂肪组织活检也在剖宫产期间从正常肥胖妊娠（Preg-Con）、GDM和非妊娠肥胖对照（Non-Preg-Con）受试者在妇科手术期间获得。GDM组孕前基础血浆FFA水平高于对照组（P=0.055）。胰岛素抑制FFA水平的能力下降，从早期到晚期妊娠的GDM和Preg-Con受试者，并显着低于GDM受试者相比，Preg-Con受试者随着时间的推移（P=0.025）。与Preg-Con受试者相比，GDM患者的脂肪组织胰岛素受体底物（IRS）-1蛋白水平低43%（P=0.02），磷脂酰肌醇3-激酶的p85 α亚基高出两倍（P=0.03）。过氧化物酶体增殖物激活受体-γ（PPARgamma）mRNA和蛋白质的水平在Preg-Con中降低了38%（P=0.006），在GDM受试者中降低了48%（P=0.005）。GDM组脂蛋白脂酶和脂肪酸结合蛋白-2 mRNA水平分别比Preg-Con组低73%和52%（P
Gestational diabetes mellitus (GDM) is associated with elevated postprandial free fatty acids (FFA) and insulin resistance; however, little is known about the cellular mechanisms underlying insulin resistance to suppress lipolysis during gestation. We evaluated the longitudinal changes in insulin suppression of FFA before pregnancy and in early (12-14 wk) and late (34-36 wk) gestation in obese subjects with normal glucose tolerance and in obese GDM subjects. Abdominal subcutaneous adipose tissue biopsies were also obtained during cesarean delivery from normal obese pregnant (Preg-Con), GDM, and nonpregnant obese control (Non-Preg-Con) subjects during gynecological surgery. GDM subjects had higher basal plasma FFA before pregnancy (P=0.055). Insulin's ability to suppress FFA levels declined from early to late gestation in both GDM and Preg-Con subjects and was significantly less in GDM subjects compared with Preg-Con subjects over time (P=0.025). Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43% lower (P=0.02) and p85alpha subunit of phosphatidylinositol 3-kinase was twofold higher (P=0.03) in GDM compared with Preg-Con subjects. The levels of peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA and protein were lower by 38% in Preg-Con (P=0.006) and by 48% in GDM subjects (P=0.005) compared with Non-Preg controls. Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects (P