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. A central goal of diabetes research (type 1 and type 2) is to generate large numbers of functional pancreatic islets or beta-cells for replacement therapy. Therefore, a fundamental knowledge of mechanisms and factors that promote beta-cell regeneration is essential for planning strategies to preserve and enhance beta-cell mass in vivo or to generate beta-cells in vitro for transplantation. We propose to apply quantitative proteomics approaches to identify novel islet proteins involved in beta-cell proliferation in a unique mouse model, the liver-specific insulin receptor knockout (LIRKO) mouse, which exhibit 20- to 30-fold increase in beta-cell mass in response to insulin resistance. Furthermore, since LIRKO mice continue to exhibit robust islet hyperplastic responses even in the presence of normoglycemia, we will also examine the proteins in serum derived from the mutant mice by proteomic approaches. This project will utilize high sensitivity, high resolution LC-FTICR capability from the resource for comparative quantitative characterization of the pancreatic islet proteins and serum proteins from mice with liver specific knockout of insulin receptor (LIRKO). The proteomic data will serve the preliminary data for NIH R01 application as well as for future publications.
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