Although poor growth in diabetes and malnutrition is attributed to decreased utilization of nutrients, the mechanism of the defect is not known. Skeletal growth is attributed to stimulation of cartilage by somatomedins (insulin-like growth factors, IGFs), circulating factors with broad anabolic effects. IGFs appear to be generated by the liver under the control of insulin and nutritional factors. While diabetes- and nutrition-associated alterations in IGFs might direct utilization of nutrients toward or away from growth, control processes are poorly understood. A major thrust of investigation by the Applicant is directed toward the elucidation of the mechanism(s) of such regulation. However, the presumed relation of hepatic fuel metabolism to the production of IGF-l cannot be studied efficiently until the nature of regulation of IGF-I production has been delineated. Preliminary studies indicate that both transcriptional and post- transcriptional mechanisms may be involved. This proposal is designed to equip the Applicant to examine metabolic problems at a molecular level. Present administrative demands prohibit necessary hands-on experience while at Emory, and the Chairman of the Department of Molecular Physiology and Biophysics at Vanderbilt has agreed to serve as """"""""Host"""""""" for appropriate training. A systematic analysis will be conducted to determine whether synthesis of IGF-I is regulated at the translational, post-transcriptional or transcriptional level. The Host laboratory has established all the assays necessary to do these studies. The application of these techniques should provide new understanding of fundamental aspects of hepatic IGF metabolism, and the experience will provide the background for the Applicant to pursue the studies central to his own research.
