Qiao Liping, Wattez Jean-Sebastien, Lee Samuel, Nguyen Amanda, Schaack Jerome, Hay William W, Shao Jianhua
Department of Pediatrics, University of California, San Diego, La Jolla, CA.
Department of Microbiology, University of Colorado School of Medicine, Aurora, CO.
Diabetes. 2017 May;66(5):1126-1135. doi: 10.2337/db16-1096. Epub 2017 Jan 10.
Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout ( ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in dams. Adiponectin reconstitution abolished these metabolic defects in dams. Hepatic glucose and triglyceride production rates of dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.
在妊娠期糖尿病（GDM）患者中，广泛观察到脂联素水平低下的情况。为了研究脂联素水平低下在妊娠期糖尿病中的因果作用，将脂联素基因敲除（ ）小鼠和野生型（WT）小鼠进行杂交，以产生有或没有脂联素缺乏的妊娠小鼠模型。在妊娠晚期，使用腺病毒载体介导的体内转导来重建脂联素。结果显示， 代母鼠在妊娠晚期出现葡萄糖不耐受和高脂血症。在 代母鼠中检测到胎儿体重增加。脂联素的重建消除了 代母鼠的这些代谢缺陷。 代母鼠的肝脏葡萄糖和甘油三酯生成率显著高于野生型代母鼠。在 代母鼠的性腺脂肪中发现脂解作用明显增强。有趣的是， 代母鼠和野生型代母鼠代谢活跃组织中胰岛素诱导的葡萄糖处置和胰岛素信号传导水平相似，这表明母体脂联素缺乏不会降低胰岛素敏感性。然而，在 代母鼠中观察到血清胰岛素浓度显著降低。此外，与野生型代母鼠相比， 代母鼠的β细胞量显著减少，但葡萄糖刺激的胰岛素释放没有减少。总之，这些结果表明脂联素在控制母体对妊娠的代谢适应中起重要作用。
