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.
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