O-GLCNAC MODIFICATION OF SIGNALING EFFECTORS IN 3T3-L1 NORMAL VS INSULIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In many models of hyperglycemia induced insulin resistance, a signaling defect at the level of insulin stimulated Akt activation has been demonstrated. Increased levels of O-GlcNAc have been causally linked to insulin signaling defects, but the specific proteins and sites of modification mediating these negative effects are not known. PI 3-kinase is upstream of Akt activation. Potentially, increased O-GlcNAc in the insulin resistant state on molecules involved in this pathway influence insulin signals. The O-GlcNAc modification state of molecules involved in this pathway (e.g. Akt, and PDK1) in normal vs. insulin resistant states will be examined. If specific proteins are found to be modified, site mapping analysis will be performed using a technique (BEMAD) newly developed at the UCSF mass spec facility. Ultimately, mapped sites will be tested for regulatory functions in the context of insulin signaling.