Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats.
Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats.
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DOI：
10.1038/s41598-023-28584-2
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发表时间：
2023-02-15
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
胎儿生长受限（FGR），随后是出生后早期追赶生长，与代谢功能障碍的风险增加有关，包括人类2型糖尿病。本研究旨在确定FGR和出生后早期追赶生长对2型糖尿病发病机制的影响，特别关注葡萄糖耐量、胰岛形态和纤维化，并利用蛋白质组学分析阐明其机制。采用Ameroid缩窄器（AC）诱发轻度宫内低灌注的方法建立FGR大鼠模型。在妊娠第17天，将AC固定在双侧子宫和卵巢动脉上，与假手术幼崽相比，导致出生体重降低20.9%。在出生后第4天（P4），将幼仔分配至营养良好（GN）组（每只母兽5只幼仔）以确保出生后追赶生长，或营养不良组（每只母兽15只幼仔）以维持较低体重。断奶后，所有幼仔均随意喂食常规饲料（P21）。两个FGR组的大鼠均出现葡萄糖耐受不良;然而，FGR良好营养（FGR-GN）组的雄性大鼠也出现高脂血症和伴有纤维化的畸形胰岛。对胰腺中表达的蛋白质的全面和功能分析表明，FGR，其次是早期追赶生长，严重加剧了雄性后代中细胞粘附相关蛋白的表达。因此，FGR和早期追赶生长引起胰岛形态异常和纤维化，与细胞粘附相关蛋白表达的紊乱有关。这些变化可能会诱发雄性大鼠的葡萄糖耐受不良和血脂异常。
Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats.
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影响因子：
2.9
作者：
DUMM, CLAG;SEMINO, MC;GAGLIARDINO, JJ
通讯作者：
GAGLIARDINO, JJ
DOI：
10.1152/ajpregu.90497.2008
发表时间：
2009-08-01
影响因子：
2.8
作者：
Bol, V. V.;Delattre, A-I.;Remacle, C.
通讯作者：
Remacle, C.
影响因子：
8.3
作者：
Alexander, BT
通讯作者：
Alexander, BT
影响因子：
4
作者：
Bowe, James E.;Franklin, Zara J.;Jones, Peter M.
通讯作者：
Jones, Peter M.
影响因子：
7.7
作者：
Barker, DJP;Eriksson, JG;Osmond, C
通讯作者：
Osmond, C