Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods.
Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods.
复制标题
对妊娠期和哺乳期喂养低蛋白饮食的母亲所生的后代的有缺陷的大鼠胰腺β细胞功能进行编程。
作者：
W. Heywood;N. Mian;P. Milla;K. Lindley
胎儿和婴儿营养不良与以后的葡萄糖耐量受损有关。我们在大鼠模型中研究了妊娠期和哺乳期蛋白质缺乏的影响，发现营养不良“程序”胰腺β细胞GK（葡萄糖激酶;称为葡萄糖传感器）和葡萄糖刺激的胰岛素分泌反应在新生儿，哺乳期和成年大鼠后代。将妊娠雌性大鼠分为3组：对照组（20%）、低蛋白（6%）组（LP-G + S组）和低蛋白组（LP-G组）。与对照组相比，LP-G + S组的新生儿和3周龄后代的脉冲式葡萄糖刺激的胰岛素分泌反应被急性破坏，胰岛素分泌峰值显著降低。此外，与对照组相比，LP-G + S组的成年动物和LP-G组的3周龄和成年后代的脉动分泌反应也发生了变化。免疫印迹法检测，与对照组相比，LP-G + S组和LP-G组的新生仔鼠和3周龄仔鼠的GK蛋白水平均降低。GK的Km和Vmax发生改变。产前和产后LP饮食似乎有一个永久性的影响，增加GK的亲和力葡萄糖（Km值下降）和降低Vmax。这表明GK功能编程的关键时期是出生后和出生后断奶期间，因为LP-G + S组的成年后代在喂食正常蛋白质饲料时，酶的Km值没有逆转。在LP-G组成年后代中进行的类似实验显示，GK的Km值在3周龄时恢复正常。总之，胎儿和婴儿营养“计划”对胰腺β细胞功能产生了不利影响;这一时期的营养不良对后代的葡萄糖稳态机制造成了不可逆转的影响，这可能使后代在以后的生活中易患糖尿病。
Poor fetal and infant nutrition has been linked to impaired glucose tolerance in later life. We studied the effect of protein deficiency during gestation and the suckling period in a rat model and found that poor nutrition 'programmes' pancreatic beta-cell GK (glucokinase; known as the glucose sensor) and glucose-stimulated insulin secretion response in newborn, suckling and adult rat offspring. Pregnant female rats were divided into three groups: a control group was kept on a normal protein (20%) diet, another group was fed a low-protein (LP) (6%) diet during gestation and suckling periods (LP-G + S group) and another was fed a LP diet during gestation then a normal protein diet during the suckling period (LP-G group). The pulsatile glucose-stimulated insulin secretion response was acutely disrupted and the peak insulin secretion was markedly decreased in newborn and 3-week-old offspring of the LP-G + S group compared with the control group. Also, there was an altered pulsatile secretory response in adults of the LP-G + S and 3-week-old and adult offspring of the LP-G groups compared with the control group. GK protein levels, detected by Western blotting, were decreased in newborn and 3-week-old offspring of both LP-G + S and LP-G groups compared with the control groups. The Km and Vmax of GK were altered. The prenatal and postnatal LP diet appeared to have a permanent effect in increasing the affinity of GK for glucose (indicated by decreased Km values) and decreasing the Vmax. This showed that the critical period of programming of the function of GK was after birth and during the postnatal weaning period, since the adult offspring of the LP-G + S group when fed a normal protein diet showed no reversal in the Km values of the enzyme. Similar experiments in adult offspring of the LP-G group showed normalization of the Km values of GK at 3 weeks of age. In conclusion, fetal and infantile nutrition 'programmes' pancreatic beta-cell function; poor nutrition during this period caused irreversible effects on glucose homoeostatic mechanisms in the offspring, which may predispose the offspring to diabetes in later life.
影响因子：
16
作者：
Leibiger, B;Leibiger, IB;Berggren, PO
通讯作者：
Berggren, PO
培养的大鼠胰岛细胞中 GLUT-1 和 GLUT-2 葡萄糖转运蛋白亚型的表达和功能。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tal,M;Liang,Y;Najafi,H;Lodish,HF;Matschinsky,FM
通讯作者：
Matschinsky,FM