Fetal growth retardation (SGA) is a serious complication of many pregnancies. The cellular and molecular mechanisms underlying growth retardation are unknown. Our laboratory has characterized a model of asymmetric growth retardation (brain growth normal and somatic growth diminished) in the fetal rat that mimics the condition in the human. Several metabolic variables are decreased in the SGA fetus including glucose, insulin, and IGF-I levels. Glucose is a vital substrate for the fetus, and limitation of its cellular availability may be one factor that causes growth retardation. Brain sparing in the SGA fetus may be a result of normal provision of glucose to cells, even though overall levels of glucose are low. Glucose transporters are proteins that (Glut) facilitate the entry of glucose into the cell. In previous studies we have found that Glut 1 function (glucose uptake) and expression (Glut 1 protein and mRNA) were diminished in lung and muscle and normal in brain. We hypothesize that: 1) glucose transport is modulated by several factors such as glucose, insulin, IGF-I and cAMP in a tissue-specific manner in the normal fetus; such modulation potentially involves mechanisms related to the expression and function of the Glut protein; 2) modulation of glucose transport is impaired in SGA lung and muscle, and that this impairment results in decreased glucose uptake in these tissues; 3) the modulation account for the phenomenon of normal glucose transport in brain to organ, and these differences in modulation account for the phenomenon of normal glucose transport in brain of SGA fetuses. We will test these hypotheses by determining the effects of glucose, insulin, IGF-I and cAMP on glucose uptake , levels of Glut 1 protein and mRNA, Glut 1 MRNA stability, and transcription rate of Glut 1 in normal and SGA fetal rat brain, lung, and muscle. We will also measure the function and numbers of insulin and IGF-I receptors in normal and SGA brain, lung, and muscle to determine if differences exist in these measurements between these organs in normal and SGA fetal rats.
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