METABOLIC ADAPTATION AND CONTROL OF LACTATION IN HUMANS

在过去的二十年里，人们重新对 母乳喂养在美国和西欧已经出现。人乳 被普遍认为是婴儿和母乳喂养的理想食品 对母亲、婴儿和他们的孩子都有真实的和潜在的好处。 关系 在美国，只有50%的女性选择 母乳喂养他们的婴儿，尽管所有的真实的和潜在的 对婴儿和母亲都有好处。 其中一些妇女 尝试母乳喂养不成功（乳汁不足 综合征）和其他已知的高风险母乳喂养 失败（有早产儿的妇女和少女母亲）。 主 牛奶体积的决定因素是乳糖产量。 如果我们能 了解调节乳糖生产的因素，我们可能会 更好地为个人设计干预策略 努力成功母乳喂养。 本提案旨在 确定母乳喂养对女性代谢的影响， 以确定乳糖和激素的代谢前体 调节乳糖合成的底物因子，乳糖合成的主要决定因素， 人的乳汁量。 需要检验的两个主要假设是： 1. 乳糖生产对碳水化合物的需求导致 在母体葡萄糖产生中和/或通过 增加的脂解和生酮，2. 葡萄糖和半乳糖 人乳糖部分来源于 乳房，这一过程是由激素和底物调节 空房的 为了验证第一个假设， 将对对照组妇女进行研究，以确定：a） 母体葡萄糖的产生和胚胎的发生在两种情况下都增加， 与非哺乳期妇女相比时的进食和禁食状态;和B） 脂解和生酮的速率增加（加速 空腹状态）与非哺乳期相比， 妇女 第二个假设将采用一个几乎 在三个不同方案中进行相同的研究设计。 中的第一 这些，我们将确定是否有很大一部分的葡萄糖 而母乳中的半乳糖乳糖是由碳源 除了血糖。 在第二部分中，我们将确定 rhGH处理7天增加：a.两组大鼠的肝细胞再生 哺乳期和非哺乳期妇女和B.乳糖（牛奶）生产， 一部分是通过增加乳房的再生。 在决赛中 协议，我们将确定是否输注氨基酸或葡萄糖 在12小时内，将分别增加或减少， 乳腺组织中来源于乳腺异生的半乳糖碳分数 哺乳期妇女 了解哺乳的代谢后果 对母体代谢和乳糖合成的调节， 对母乳生产调节的新见解，因此， 提供新的战略，以提高成功的数量， 母乳喂养的妇女，并帮助那些在过去有 挣扎和/或失败的母乳喂养他们的婴儿。 这反过来又 将对健康和经济产生重大影响。

Over the last two decades, renewed interest and expertise in and about breastfeeding has occurred in the U.S. and Western Europe. Human milk is universally accepted as the ideal food for infants and breastfeeding has real and potential benefits for the mother, the infant and to their relationship. In the United States only 50 percent of women choose to breastfeed their infants despite all of the real and potential advantages to both the infant and mother. A number of these women have been unsuccessful in their attempts to breastfeed (insufficient milk syndrome) and others are known to be at high risk of breastfeeding failure (women with premature infants and teenage mothers). The primary determinant of milk volume is lactose production. If we could understand the factors which regulate lactose production, we might be better able to design interventional strategies for individuals struggling to breastfeed successfully. The present proposal is designed to determine the metabolic consequences of breastfeeding in women and to determine the metabolic precursors of lactose and the hormone substrate factors regulating lactose synthesis, a major determinant of milk volume in humans. The two overriding hypotheses to be tested are: 1. The carbohydrate demands of lactose production result in an increase in maternal glucose production and/or a sparing of maternal glucose by increased lipolysis and ketogenesis, 2. The glucose and galactose in human lactose are partially derived from gluconeogenesis within the breast, and this process is regulated by both hormones and substrate availability. To test the first hypothesis eight lactating and eight control women will be studied to determine whether: a) the rates of maternal glucose production and gluconeogenesis are increased in both the fed and fasted state when compared to non-lactating women; and b) the rates of lipolysis and ketogenesis are increased (an accelerated state of fasting) in the nursing mothers when compared to non-lactating women. The second hypothesis will be tested employing a nearly identical study design in three separate protocols. In the first of these, we will determine whether a significant portion of the glucose and galactose in breast milk lactose is derived from sources of carbon other than plasma glucose. In the second one, we will determine whether rhGH treatment for 7 days increases: a. Hepatic gluconeogenesis in both lactating and non-lactating women and b. lactose (milk) production, in part, by increasing gluconeogenesis in the breast. In the final protocol, we will determine if an infusion of amino acids or of glucose for a period of 12 hrs will increase or decrease, respectively, the fraction of galactose carbon derived from gluconeogenesis in breast of lactating women. Understanding the metabolic consequences of lactation on maternal metabolism and the regulation of lactose synthesis will give new insights into the regulation of human milk production, thus, providing new strategies to improve the number of successfully breastfeeding women and to help those women who in the past have struggled and/or failed breastfeeding their infants. This, in turn, will have significant health and economic impact.