Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat

Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat
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DOI:
10.1007/s001250051038
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发表时间:
1998-09-01
期刊:
影响因子:
8.2
通讯作者:
Bréant, B
Bréant, B
中科院分区:
医学1区
文献类型:
--
作者:
Garofano, A;Czernichow, P;Bréant, B

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我们最近发现,大鼠妊娠后期母亲的食物限制会降低后代出生时的β细胞质量,但不会改变β细胞增殖。目前工作的目的是确定:1​​)母亲持续营养不良直至断奶(R组)是否会更显着地改变后代的β细胞质量,以及从断奶到成年的正常食物供应是否可以逆转有害影响; 2) β 细胞增殖的改变是否是导致 β 细胞质量减少的原因。在R动物和年龄匹配的对照(C组)中,在哺乳期和断奶后随意喂养的成年期测定β细胞分数和增殖能力。在第 21 天,由食物限制母亲(R 动物)出生和哺乳的后代的 β 细胞质量和数量减少了 66%,尽管 β 细胞增殖保持正常,但从出生到断奶,其数量和数量没有增加。 3 个月大时,R 动物的 β 细胞分数减少了 35%,其中胰头减少了 50%。在该区域,β细胞增殖与对照组相似。与对照组相比,胰腺尾部的 β 细胞分数仅略有受损,但 β 细胞增殖增加了 37%。与这些 R 动物的胰头相比,这种增加与胰岛大小分布向中型和大型胰岛的转变有关。在成年对照动物中未观察到β细胞分数、增殖或胰岛大小分布的区域差异。总之,断奶前长期营养不良会损害 β 细胞发育,但不会损害 β 细胞增殖。随后的再营养会导致β细胞增殖增加,但这不足以完全恢复β细胞质量。
We have recently shown that maternal food restriction during late pregnancy in rats decreased beta-cell mass in the offspring at birth, without altering beta-cell proliferation. The aim of the present work was to determine: 1) whether sustained maternal undernutrition until weaning (R group) more dramatically alters beta-cell mass in the offspring and if normal food supply from weaning until adulthood could reverse the deleterious effects and; 2) if altered beta-cell proliferation was responsible for the decreased beta-cell mass. Beta-cell fraction and proliferative capacity were determined during the suckling period and at adult age after ad libitum feeding from weaning in the R animals and in age-matched controls (C group). At day 21, the offspring born and nursed by food-restricted mothers (R animals) showed a 66% reduction in beta-cell mass and number, which did not increase from birth to weaning, although beta-cell proliferation remained normal. At 3 months of age, R animals had 35% decreased beta-cell fraction, with a 50% decrease in the head of the pancreas. In that area, beta-cell proliferation was similar to that of the controls. In the tail of the pancreas, beta-cell fraction was only slightly impaired but beta-cell proliferation was increased by 37%, as compared with the controls. This increase was associated with a shift in islet size distribution towards medium and large islets compared with the head of pancreas from these R animals. No regional variations of beta-cell fraction, proliferation or islet size distribution were observed in adult control animals. In conclusion, prolonged malnutrition until weaning impairs beta-cell development but not beta-cell proliferation. Subsequent re-nutrition is followed by increased beta-cell proliferation but this is insufficient to fully restore beta-cell mass.