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Pilot Study on Examination of LIRKO Islets and Serum Using Quantitative Proteomic Approaches


EMSL Project ID
17390

Abstract

A central goal of diabetes research (type 1 and type 2) is to generate large numbers of functional islets or -cells for replacement therapy. Therefore, a fundamental knowledge of mechanisms and factors that promote -cell regeneration is essential for planning strategies to preserve and enhance -cell mass in vivo or to generate -cells in vitro for transplantation. We propose to apply quantitative proteomics approaches to identify novel islet proteins involved in -cell proliferation in a unique mouse model, the liver-specific insulin receptor knockout (LIRKO) mouse, which exhibit 20- to 30-fold increase in -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.

Project Details

Start Date
2006-03-01
End Date
2009-03-01
Status
Closed

Team

Principal Investigator

Rohit Kulkarni
Institution
Joslin Diabetes Center

Team Members

Vladislav Petyuk
Institution
Pacific Northwest National Laboratory

Weijun Qian
Institution
Pacific Northwest National Laboratory

Related Publications

[1] Zhou, J.Y.; Petritis, B.O.; Petritis, K.; Norbeck, A.D.; Weitz, K.; Moore, R.J.; Camp, D.G.; Kulkarni, R.; Smith, R.D. and Qian, W.J. Mouse-Specific Tandem IgY7-SuperMix Immunoaffinity Separations for Improved LC-MS/MS Coverage of the Plasma Proteome. J. Proteome Res., 2009, [Epub ahead of print]
Zhang, X.; Zhou, J.Y.; Chin, M.H.; Schepmoes, A.A.; Petyuk, V.A.; Weitz, K.K.; Petritis, B.O.; Monroe, M.E.; Camp, D.G.; Wood, S.A.; Melega, W.P.; Bigelow, D.J.; Smith, D.J.; Qian, W.J.- and Smith, R.D. Region-specific protein abundance changes in the brain of MPTP-induced Parkinsons disease mouse model. J Proteome Res, 2010, 9, 1496-1509