ROLE OF HYPERINSULINEMIA IN MACROSOMIC INFANTS BORN TO DIABETIC MOTHERS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。妊娠期糖尿病(GDM)发生在所有妊娠的1-3%，众所周知，它会增加胎儿、新生儿和母亲的发病率和死亡率。在过去的20年里，对产妇高血糖的更好控制，大大降低了与糖尿病妊娠相关的总死亡率和发病率。尽管妊娠期糖尿病合并巨大儿的发生率随着妊娠期高血糖的严格控制而下降，但它仍然是围产期医学中的一个主要保健问题。巨大儿主要发生在对胰岛素敏感的组织，并与高胰岛素血症有关。尽管有很强的相关临床和流行病学数据，但胰岛素导致巨大儿的机制仍然是个谜。最近的数据表明，胰岛素是法尼化p21RAS数量的主要调节者，而法尼化p21RAS反过来又显著增加细胞对各种有丝分裂原的反应。妊娠期糖尿病巨大儿可能是高胰岛素血症对p21RAs细胞法尼化的刺激性影响的结果。这项研究的数据可能有助于阐明高胰岛素血症导致糖尿病母亲所生婴儿巨大儿的可能机制。在未来，这也可能导致通过使用法尼基转移酶抑制剂或更密切地关注胰岛素血症水平来预防巨大儿。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gestational Diabetes Mellitus (GDM) occurs in 1-3% of all pregnancies and is well known to increase morbidity and mortality in the fetus, the neonate and the mother. Better control of maternal hyperglycemia in the last 20 years has resulted in a significant reduction of the overall mortality and morbidity associated with diabetic pregnancies. Even though the incidence of fetal macrosomia associated with GDM has decreased with strict control of maternal hyperglycemia during pregnancy, it remains a major health care problem in perinatal medicine. Fetal macrosomia occurs mainly in insulin-sensitive tissues and is associated with hyperinsulinemia. Despite the strong correlative clinical and epidemiologic data, the mechanism whereby insulin can cause macrosomia remains enigmatic. Recent data suggests that insulin is a major regulator of the amount of farnesylated p21 Ras, which in turn significantly increases the cellular response to various mitogens. Fetal macrosomia in gestational diabetes may represent the consequences of the stimulatory influence of hyperinsulinemia on the cellular amount of farnesylated p21 Ras. The data from this study may help elucidate a possible mechanism by which hyperinsulinemia leads to macrosomia in the infants born the diabetic mothers. In the future this may also lead to prevention of macrosomia through the use of farnesyltrasferase inhibitors or closer attention to the levels of insulinemia.