Carbohydrate regulated genes provide a mechanism for integrating cellular responses with resource utilization in the entire body. This coordinated effort provides exquisite regulation in maintaining the circulating levels of glucose in humans within a fairly narrow range. Glucose deprivation increases the rate of glucose transport by the GLUT-1 receptor in a number cel types by a protein synthesis dependent mechanism. However, the expression of the GLUT1 glucose transporter does not change. This proposal focuses on the discovery of a unique 50 kDa protein whose synthesis is regulated by glucose availability. The studies proposed test the hypothesis that this 50 Kda protein modulates the activity of GLUT 1 to affect changes in glucose uptake. The research plan involves a series of specific aims which define the expression of the p50 protein at the transcriptional and translational level in 3T3-L1 adipocytes and the mouse. Experiments are designed to examine the interaction of p50 with GLUT! and the effect of that interaction on transport activity. Finally, studies are proposed to examine the role of p50 in transport function, in vivo, using antisense technology to inhibit it expression and adenovirus transduction system to stimulate overexpression.
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