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Proteomic Studies of type 2 diabetes using knockout mouse models


EMSL Project ID
47738

Abstract

This is an NIH-funded R01 project on diabetes research. A central goal of diabetes research (type 1 and type 2) is to generate large numbers of functional 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 is let 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-MS 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).

Project Details

Start Date
2012-12-03
End Date
2015-03-17
Status
Closed

Team

Principal Investigator

Weijun Qian
Institution
Pacific Northwest National Laboratory

Co-Investigator(s)

Marina Gritsenko
Institution
Pacific Northwest National Laboratory

Team Members

Rohit Kulkarni
Institution
Joslin Diabetes Center