A Low Dose of Ouabain Alters the Metabolic Profile of Adult Rats Experiencing Intrauterine Growth Restriction in a Sex-Specific Manner
A Low Dose of Ouabain Alters the Metabolic Profile of Adult Rats Experiencing Intrauterine Growth Restriction in a Sex-Specific Manner
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DOI：
10.1007/s43032-022-01118-3
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发表时间：
2022-11-04
影响因子：
2.9
通讯作者：
Chen，Liang
中科院分区：
文献类型：
--
作者：
Yue，Jing;Wu，Han;Chen，Liang
宫内生长受限（IUGR）增加了2型糖尿病（T2 DM）和代谢性疾病的风险。IUGR胎儿的胰腺通常以胰腺发育不良和β细胞复制减少引起的胰岛素分泌水平降低为特征。以往的研究表明，低剂量哇巴因可减少IUGR时胚胎肾细胞的凋亡，部分恢复出生时肾单位的数量。获救的肾脏功能良好，降低了高血压的患病率。因此，我们假设哇巴因可以挽救胎儿宫内发育迟缓期间的胰腺发育，并降低2型糖尿病和代谢性疾病的发病率。采用母体营养不良诱导IUGR大鼠模型，并在妊娠期给予低剂量哇巴因。在整个实验过程中，我们监测了体重增加的模式，并评估了不同阶段后代的代谢参数。IUGR组中的雄性而非雌性后代呈现追赶性生长。哇巴因可以改善男性后代糖耐量受损的情况;然而，这种理想的效果因衰老而消失。胰岛素敏感性显着受损的IUGR男性后代，但哇巴因改善，即使在老年。然而，在雌性后代中，低出生体重似乎是一个有益的因素，即使在老年;管理哇巴因加剧了这些有利的影响。我们的数据表明，IUGR影响葡萄糖代谢的性别特异性的方式和哇巴因治疗在怀孕期间产生强烈对比的影响，在男性和女性大鼠。
Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes mellitus (T2DM) and metabolic diseases. The pancreas of fetuses with IUGR is usually characterized by pancreatic dysplasia and reduced levels of insulin secretion caused by the diminished replication of β-cells. Previous studies showed that a low dose of ouabain could reduce the apoptosis of embryonic nephric cells during IUGR and partially restore the number of nephrons at birth. The rescued kidneys functioned well and decreased the prevalence of hypertension. Thus, we hypothesized that ouabain could rescue pancreatic development during IUGR and reduce the morbidity of T2DM and metabolic diseases. Maternal malnutrition was used to induce the IUGR model, and then a low dose of ouabain was administered to rats with IUGR during pregnancy. Throughout the experiment, we monitored the pattern of weight increase and evaluated the metabolic parameters in the offspring in different stages. Male, but not female, offspring in the IUGR group presented catch-up growth. Ouabain could benefit the impaired glucose tolerance of male offspring; however, this desirable effect was eliminated by aging. The insulin sensitivity was significantly impaired in male offspring with IUGR, but it was improved by ouabain, even during old age. However, in the female offspring, low birth weight appeared to be a beneficial factor even in old age; administering ouabain exacerbated these favorable effects. Our data suggested that IUGR influenced glucose metabolism in a sex-specific manner and ouabain treatment during pregnancy exerted strongly contrasting effects in male and female rats.