Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring
Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring
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DOI：
10.1152/ajpregu.00206.2004
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发表时间：
2005-02-01
影响因子：
2.8
通讯作者：
Ozanne, SE
中科院分区：
文献类型：
--
作者：
Fernandez-Twinn, DS;Wayman, A;Ozanne, SE
成人疾病如心血管疾病、高血压和2型糖尿病在流行病学上与胎儿生长发育不良有关。在妊娠期和哺乳期饲喂低蛋白（LP）饮食的大鼠母鼠的雄性后代发生糖尿病，伴随着胰岛素信号传导机制的改变。这种关联尚未在雌性后代中进行过研究。这项研究的目的是确定女性LP后代是否在以后的生活中患上糖尿病。对照组和LP雌性后代组分别来自在整个妊娠期和哺乳期饲喂对照（20%蛋白质）或等热量（8%蛋白质）饲料的大鼠母体。两组均断奶，并维持20%正常实验室食物，直到21个月大时，他们进行静脉葡萄糖耐量试验（IVGTT）。两组的空腹血糖相当，但LP空腹胰岛素约为对照组的2倍（P < 0.02）。IVGTT期间两组的葡萄糖耐量相当;然而，4分钟时LP血浆胰岛素峰值约为对照组的3倍（P < 0.001）。LP组血浆胰岛素曲线下面积是对照组的1.9倍（P < 0.02）。在Western印迹中，肌肉蛋白激酶C-zeta表达和腹部脂肪中p110 β相关的p85 α在LP中均降低（P < 0.05）。对葡萄糖刺激的高胰岛素血症加上某些胰岛素信号分子的衰减意味着LP肌肉和脂肪中胰岛素抵抗的发展。这些观察结果表明，宫内蛋白限制导致老年女性胰岛素抵抗，因此增加了2型糖尿病的风险。
Human adult diseases such as cardiovascular disease, hypertension, and type 2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low-protein ( LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin-signaling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine whether female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet, respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 mo of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the two groups; however, LP fasting insulin was approximately twofold that of controls (P < 0.02). Glucose tolerance during IVGTT was comparable between the two groups; however, LP peak plasma insulin at 4 min was approximately threefold higher than in controls (P < 0.001). LP plasma insulin area under the curve was 1.9-fold higher than controls (P < 0.02). In Western blots, both muscle protein kinase C-zeta expression and p110 beta-associated p85 alpha in abdominal fat were reduced (P < 0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin-signaling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and, hence, an increased risk of type 2 diabetes.