IBN-9512315 Garofalo, Robert S. The hormone, insulin, exerts its effects on cells by binding to a cell surface protein called the insulin receptor. This binding causes the receptor to transmit signals into the interior of the cell which result in glucose uptake and other metabolic changes. While a great deal about the structure of the insulin receptor is known, there is limited information about the nature of the signals transmitted within the cell or the components of the signaling pathway. The studies proposed by Dr. Garofalo use an excellent model system to study the mechanism of action of the insulin receptor. The model offers advantages over other experimental systems, notably the ability to easily generate and characterize mutations, and to study the effects of mutations on the function of the insulin receptor in a complex organism. Using this system, the function of the insulin receptor in the development of the nervous system and muscles, and in the regulation of growth will be examined. The proposed studies will also identify novel cellular components involved in the function of the receptor. The elucidation of these components in this model system is simplified by its ability to be modified genetically and characterized biochemically. The identification of components in the insulin receptor signaling pathway is significant for our understanding of the pathogenesis and treatment of diseases, such as diabetes and cancer, and may suggest novel targets for intervention.
