Chamson-Reig Astrid, Thyssen Sandra M, Arany Edith, Hill David J
Lawson Health Research Institute, St Joseph's Health Care, 268 Grosvenor Street Room H404, London, Ontario, Canada N6A 4V2.
J Endocrinol. 2006 Oct;191(1):83-92. doi: 10.1677/joe.1.06754.
Restriction of dietary protein during gestation and lactation in the rat results in a reduction in beta cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 microm(2)) and medium (between 5000 and 10 000 microm(2)) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of beta cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in mid-gestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both beta cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of beta cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of beta cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.
在大鼠妊娠和哺乳期限制饮食中的蛋白质，会导致其后代的β细胞数量、胰岛素含量及释放减少，且后代成年后会出现葡萄糖不耐受。本研究旨在确定在产前发育过程中是否存在一个特定的发育窗口期，在此期间内分泌胰腺的发育最易受到营养损伤的影响。怀孕大鼠从受孕到分娩期间接受低蛋白（8%，LP）但热量相等的饮食，分别在妊娠的前2周（LP(1 - 2)）、仅在第二周（LP(2)）或第三周（LP(3)）。在其他时间，它们接受20%蛋白质（C）的饮食，而对照动物则持续接受这种饮食。当后代在130日龄时接受检查，与喂食对照饮食的动物相比，接受LP饮食的动物葡萄糖耐量显著受损。在出生后第1天和第21天检查后代的胰腺形态。对于所有LP处理，LP饮食导致出生后第1天存在的大（超过10000平方微米）和中等（5000至10000平方微米之间）大小胰岛的数量显著减少。因此，平均胰岛面积和β细胞的平均数量减少。LP饮食的影响在雌性的LP(2)组和雄性的LP(3)组中最为明显，且比持续暴露于LP的情况更严重。LP在妊娠早期和晚期对胰岛素和Glut - 2 mRNA表达产生负面影响，但在妊娠中期给予后表达增加。LP处理未改变胰腺总胰岛素含量。Pdx - 1是一种与β细胞发育和胰岛素基因转录相关的转录因子，在LP(1 - 2)和LP(3)处理后的雌性后代中减少，但在雄性后代中未减少。所有LP处理均降低了胰岛中巢蛋白mRNA的胰腺表达以及巢蛋白免疫反应性细胞的丰度。到出生后第21天，平均胰岛面积和β细胞数量在很大程度上已恢复。然而，暴露于LP饮食的后代中胰岛素和Glut - 2 mRNAs升高，尤其是在雌性后代中。研究表明，妊娠早期、中期或晚期的LP饮食损伤，均会因未能发育出更大的胰岛而导致出生后β细胞相对不足，但雌性在妊娠中期尤其易感，而雄性在妊娠晚期尤其易感。
