PLACENTAL LACTOGEN AND FETAL DEVELOPMENT

该实验室最近的研究表明胎盘催乳素的作用 (PL)和催乳素在控制胎儿和新生儿胰岛素产生中的作用 在葡萄糖依赖型胰岛素分泌的出现中 围产期。阐明催乳激素在围产儿中的作用 我们提出了两个具体的目标：第一个目标是 乳素抵抗对胰岛细胞的影响 胚胎、新生和出生后小鼠的发育和胰岛素产生。 催乳素(催乳素)缺乏的抗催乳素小鼠 受体已经从保罗·凯利博士那里获得。我们假设 胰腺催乳素受体(PRLRs)的缺失将使 小鼠PL和催乳素在胰腺中的生物活性 减少胰岛β细胞质量、胰岛素产生和葡萄糖依赖胰岛素 围产期的分泌物。第二个目标是探索 催乳素调节胰岛素产生和分泌的细胞机制 胎鼠和出生后小鼠的分泌物。研究将集中在以下几个方面 葡萄糖转运、葡萄糖代谢和细胞内钙内流 催乳激素的胰岛素调节作用。表达的个体发生学 β细胞谷氨酸氨基转移酶、葡萄糖激酶和电压依赖性钙通道 葡萄糖转运、葡萄糖氧化和钙内流的速率 PRLR缺陷小鼠将与正常对照小鼠在 不同的发展阶段。那么PL和催乳素对心脏功能的影响。 葡萄糖转运、葡萄糖利用、钙摄取及其表达 Glut2、葡萄糖激酶和电压依赖性钙通道 在分离的胚胎、新生和出生后小鼠的胰岛中进行检查。 最后，我们将检查葡萄糖转运抑制剂的效果， 糖代谢和钙内流对胰岛素抵抗作用的影响 胎儿和出生后胰岛中的催乳激素。我们假设 催乳素通过以下两种途径发挥急性和慢性胰岛素样作用 葡萄糖依赖和非葡萄糖依赖的机制导致β 细胞内钙内流。这些研究的结果应该澄清这些角色 催乳素在控制围产期和产后胰岛素生成中的作用 为探讨巨大儿的发病机制提供了新的思路。 糖尿病母亲的婴儿。

Recent studies from this laboratory implicate roles of placental lactogen (PL) and prolactin in the control of fetal and neonatal insulin production and in the emergence of glucose-dependent insulin secretion in the perinatal period. To clarify the roles of lactogenic hormones in perinatal insulin production, we propose two specific aims: The first objective is to examine the effects of lactogen resistance on pancreatic islet cell development and insulin production in fetal, neonatal and postnatal mice. Lactogen resistant mice that are deficient in lactogenic (prolactin) receptors have been obtained from Dr. Paul Kelly. We hypothesize that the absence of pancreatic prolactin receptors (PRLRs) will abolish the biological activity of mouse PL and prolactin in the pancreas and thereby reduce beta cell mass, insulin production and glucose-dependent insulin secretion in the perinatal period. The second objective is to explore cellular mechanisms by which lactogens regulate insulin production and secretion in fetal and postnatal mice. Studies will focus on the roles of glucose transport, glucose metabolism, and cellular calcium influx in the insulinotropic effects of lactogenic hormones. The ontogeny of expression of beta cell Glut2, glucokinase and voltage-dependent calcium channels and the rates of glucose transport, glucose oxidation and calcium influx in PRLR-deficient mice will be compared with those in normal control mice at various stages of development. Then the effects of PL and prolactin on glucose transport, glucose utilization, calcium uptake and the expression of Glut2, glucokinase and voltage-dependent calcium channels will be examined in isolated islets from fetal, neonatal and postnatal mice. Finally, we will examine the effects of inhibitors of glucose transport, glucose metabolism and calcium influx on the insulinotropic effects of lactogenic hormones in fetal and postnatal islets. We hypothesize that lactogens exert acute and chronic insulinotropic effects through both glucose-dependent and glucose-independent mechanisms that lead to beta cell calcium influx. The results of these studies should clarify the roles of lactogens in the control of perinatal and postnatal insulin production and may provide new insight into the pathogenesis of fetal macrosomia in the infant of the diabetic mother.