Center for Gender-Specific Medicine, Gender Specific Prevention and Health Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.
Acta Diabetol. 2019 Jun;56(6):681-689. doi: 10.1007/s00592-019-01304-x. Epub 2019 Feb 28.
Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy. Maternal adipose tissue and fetal membranes secrete various molecules that are relevant players in the pathogenesis of GDM. This pilot study aimed to examine whether the expression of the high mobility group box 1 protein (HMGB1) and its receptor for advanced glycation end products (RAGE), and the vasoactive intestinal peptide (VIP) and its receptors (VPAC-1,-2) were modified in pregnant women with GDM.
Fetal membranes (FMs), omental adipose tissue (VAT) explants, and serum samples were obtained from 12 women with GDM and 12 with normal glucose tolerance (NGT) at delivery. The expression of HMGB1, RAGE and VIP, VPAC-1,-2 was detected by Western Blotting in explants; circulating levels and "in vitro" release of HMGB1 and VIP were measured by ELISA tests.
HMGB1 tissue expression was higher in FMs obtained from GDM women (p = 0.02) than in FMs from NGT women. VPAC2 (p = 0.03) and RAGE (p = 0.03) tissue expressions were significantly increased in VAT from GDM subjects. Only FMs of NGT released detectable levels of HMGB1, which was not observed in samples obtained from GDM. VAT of GDM released lower levels of VIP (p = 0.05) than NGT samples.
This study indicates that a fine tuned regulation exists between FMs and VAT throughout pregnancy to maintain immune metabolic homeostasis. In GDM a balance between inflammatory and anti-inflammatory mediators has been observed. Further studies are needed to establish their exact role on fetal and maternal outcomes in GDM.
妊娠期糖尿病（GDM）被定义为在怀孕期间首次诊断出的葡萄糖不耐受。母体脂肪组织和胎儿膜分泌各种分子，这些分子是 GDM 发病机制中的重要参与者。本初步研究旨在检查 GDM 孕妇的高迁移率族蛋白 1 蛋白（HMGB1）及其晚期糖基化终产物受体（RAGE）、血管活性肠肽（VIP）及其受体（VPAC-1、-2）的表达是否发生改变。
在分娩时从 12 名 GDM 妇女和 12 名糖耐量正常（NGT）妇女中获得胎儿膜（FM）、网膜脂肪组织（VAT）外植体和血清样本。通过 Western Blotting 在外植体中检测 HMGB1、RAGE 和 VIP 的表达；通过 ELISA 试验测量循环水平和“体外”释放的 HMGB1 和 VIP。
GDM 妇女的 FM 中 HMGB1 的组织表达高于 NGT 妇女（p=0.02）。GDM 受试者的 VAT 中 VPAC2（p=0.03）和 RAGE（p=0.03）的组织表达明显增加。仅 NGT 的 FM 释放可检测水平的 HMGB1，而 GDM 样本中未观察到。GDM 的 VAT 释放的 VIP 水平低于 NGT 样本（p=0.05）。
本研究表明，在整个怀孕期间，FM 和 VAT 之间存在精细调节，以维持免疫代谢稳态。在 GDM 中，观察到炎症和抗炎介质之间的平衡。需要进一步研究以确定它们在 GDM 中对胎儿和母体结局的确切作用。
