Proteomic Studies of type 2 diabetes using knockout models
EMSL Project ID
36197
Abstract
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-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
2009-10-21
End Date
2012-10-21
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
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]
El Ouaamari A, D Kawamori, E Dirice, CW Liew, JL Shadrach, J Hu, H Katsuta, J Hollister-Lock, W Qian, AJ Wagers, and RN Kulkarni. 2013. "Liver-derived systemic factors drive ?-cell hyperplasia in insulin resistant states." Cell Reports 3(2):401-410. doi:10.1016/j.celrep.2013.01.007
Heibeck, T.H.; Ding, S.J.; Opresko, L.K.; Zhao, R.; Schepmoes, A.A.; Yang, F.; Tolmachev, A.V.; Monroe, M.E.; Camp, D.G.; Smith, R.D.; Wiley, H.S. and Qian, W.J. An Extensive Survey of Tyrosine Phosphorylation Revealing New Sites in Human Mammary Epithelial Cells. J. Proteome Res., 2009, 8(8), 3852-61
Zhang X, ME Monroe, B Chen, MH Chin, TH Heibeck, AA Schepmoes, F Yang, BO Petritis, DG Camp, II, JG Pounds, JM Jacobs, DJ Smith, DJ Bigelow, RD Smith, and W Qian. 2010. "Endogenous 3, 4- Dihydroxyphenylalanine and Dopaquinone Modifications on Protein Tyrosine: links to mitochondrially derived oxidative stress via hydroxyl radical." Molecular & Cellular Proteomics. MCP 9(6):1199-1208.
Zhou J, AA Schepmoes, X Zhang, RJ Moore, ME Monroe, JH Lee, DG Camp, II, RD Smith, and W Qian. 2010. "Improved LC-MS/MS Spectral Counting Statistics by Recovering Low Scoring Spectra Matched to Confidently Identified Peptide Sequences." Journal of Proteome Research 9(11):5698-5704. doi:10.1021/pr100508p
Zhou J, GP Dann, CW Liew, RD Smith, RN Kulkarni, and W Qian. 2011. "Unraveling pancreatic islet biology by quantitative proteomics." Expert Review of Proteomics 8(4):495-504. doi:10.1586/epr.11.39
Zhou J, GP Dann, T Shi, L Wang, X Gao, D Su, CD Nicora, AK Shukla, RJ Moore, T Liu, DG Camp, II, RD Smith, and W Qian. 2012. "Simple Sodium Dodecyl Sulfate-Assisted Sample Preparation Method for LC-MS-based Proteomic Applications." Analytical Chemistry 84(6):2862-2867. doi:10.1021/ac203394r