PI-3-kinase mediated signaling by insulin and IGF-1

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DESCRIPTION (provided by applicant): Type 2 diabetes mellitus seriously impacts on the quality of life and longevity of millions of Americans. Type 2 diabetes mellitus is caused primarily by impaired signaling by insulin. PI-3- kinase plays a crucial role in the insulin signaling pathway. This research project will better define the mechanism by which PI-3-kinase transduces the insulin signal. Preliminary evidence indicates that insulin stimulates the translocation of PI3K to discrete intracellular locations, quite distinct from the response to other growth factors. It is hypothesized that this distinct subcellular localization is partly responsible for the unique signaling effects of insulin. This will be investigated further by defining the subcellular localization of insulin-stimulated PI-3-kinase signaling, the mechanism governing this localization, and the function of this localization. It is expected that a better understanding of the signaling pathway utilized by insulin will provide insight into the pathophysiology of diabetes mellitus and identify potential targets for novel therapeutics. This project will also contribute significantly to the career development of Dr. Field. Under the mentorship of Dr. Lewis Cantley and Dr. Anne Klibanski this career development award is expected to foster Dr. Field's development into a successful independent clinician-scientist.