METABOLIC ADAPTATION AND CONTROL OF LACTATION IN HUMANS

在过去的二十年里，对和关于 母乳喂养在美国和西欧都有发生。人乳 被普遍认为是婴儿和母乳喂养的理想食物 对母亲、婴儿和他们的孩子有实际和潜在的好处 两性关系。在美国，只有50%的女性选择 母乳喂养他们的婴儿，尽管所有真实和潜在的 对婴儿和母亲都有好处。这些女性中有许多人 尝试母乳喂养(乳汁不足)失败 综合症)和其他已知的母乳喂养高危人群 失败(有早产儿的妇女和十几岁的母亲)。初级阶段 乳糖量的决定因素是乳糖产量。如果我们可以 了解调节乳糖生产的因素，我们可能会 能够更好地为个人设计干预策略 努力成功地母乳喂养。本提案是专门为 为了确定母乳喂养对妇女的代谢影响， 测定乳糖和激素的代谢前体 调节乳糖合成的底物因素是乳糖合成的主要决定因素 人体内的乳量。需要检验的两个压倒一切的假设是： 1.乳糖生产对碳水化合物的需求增加 在母体葡萄糖生产和/或节约母体葡萄糖方面 增加脂肪分解和酮类生成，2.葡萄糖和半乳糖 人的乳糖部分来源于体内的糖异生 乳房，这个过程受荷尔蒙和底物的调节 可用性。要检验第一个假设，八个人在哺乳，八个人在 将对对照妇女进行研究，以确定是否：a) 母体葡萄糖的产生和糖异生都增加了 与非哺乳期妇女相比，处于进食和禁食状态；以及 脂肪分解和酮体生成率增加(加速 空腹状态)与非哺乳期母亲的比较 女人。第二个假设将通过使用近 三种不同方案的相同研究设计。在…的第一个 这些，我们将确定是否有很大一部分葡萄糖 而母乳中的半乳糖乳糖来自碳的来源 而不是血糖。在第二个问题中，我们将确定是否 重组人生长激素治疗7天可增加：a.两组大鼠肝脏糖异生 哺乳期和非哺乳期妇女和乳糖(牛奶)生产#年。 部分是通过增加乳房中的糖异生作用。在决赛中 方案，我们将确定输注氨基酸或葡萄糖 在12小时内，将分别增加或减少 乳房糖异生形成的半乳糖碳组分 哺乳期的女性。了解哺乳期的代谢后果 对母体新陈代谢和乳糖合成的调节 对母乳生产监管的新见解，因此， 提供新的战略，以提高成功的数量 帮助哺乳妇女，帮助那些在过去 努力和/或失败地哺乳他们的婴儿。这又反过来， 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.