Urinary protein profiles in a rat model for diabetic complications
Urinary protein profiles in a rat model for diabetic complications
Diabetes mellitus is estimated to affect approximately 24 million people in the United States and more than 150 million people worldwide. There are numerous end organ complications of diabetes, the onset of which can be delayed by early diagnosis and treatment. Although assays for diabetes are well founded, tests for its complications lack sufficient specificity and sensitivity to adequately guide these treatment options. In our study, we employed a streptozotocin-induced rat model of diabetes to determine changes in urinary protein profiles that occur during the initial response to the attendant hyperglycemia (e.g. the first two months) with the goal of developing a reliable and reproducible method of analyzing multiple urine samples as well as providing clues to early markers of disease progression. After filtration and buffer exchange, urinary proteins were digested with a specific protease, and the relative amounts of several thousand peptides were compared across rat urine samples representing various times after administration of drug or sham control. Extensive data analysis, including imputation of missing values and normalization of all data was followed by ANOVA analysis to discover peptides that were significantly changing as a function of time, treatment and interaction of the two variables. The data demonstrated significant differences in protein abundance in urine before observable pathophysiological changes occur in this animal model and as function of the measured variables. These included decreases in relative abundance of major urinary protein precursor and increases in pro-alpha collagen, the expression of which is known to be regulated by circulating levels of insulin and/or glucose. Peptides from these proteins represent potential biomarkers, which can be used to stage urogenital complications from diabetes. The expression changes of a pro-alpha 1 collagen peptide was also confirmed via selected reaction monitoring.
2145-2158
Schlatzer, Daniela M.
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Dazard, Jean-Eudes
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Dharsee, Moyez
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Ewing, Rob M
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Ilchenko, Serguei
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Stewart, Ian
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Christ, George
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Chance, Mark R.
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September 2009
Schlatzer, Daniela M.
4c4f9f8b-0746-4a25-967a-729e41a58b65
Dazard, Jean-Eudes
f8129953-4050-4766-bb43-9d1fcdc59f9f
Dharsee, Moyez
f06c7ce2-562c-4570-8dd7-2b57796a0999
Ewing, Rob M
022c5b04-da20-4e55-8088-44d0dc9935ae
Ilchenko, Serguei
076b0e98-8968-4121-89e3-5583be5f4180
Stewart, Ian
11d64fb5-107f-4683-a706-39baf5fbb955
Christ, George
53f9b42f-b857-4d17-a328-9cae44607f0e
Chance, Mark R.
855fab90-5057-490a-887f-d7c1db99faf5
Schlatzer, Daniela M., Dazard, Jean-Eudes, Dharsee, Moyez, Ewing, Rob M, Ilchenko, Serguei, Stewart, Ian, Christ, George and Chance, Mark R.
(2009)
Urinary protein profiles in a rat model for diabetic complications.
Molecular & Cellular Proteomics, 8 (9), .
(doi:10.1074/mcp.M800558-MCP200).
(PMID:19497846)
Abstract
Diabetes mellitus is estimated to affect approximately 24 million people in the United States and more than 150 million people worldwide. There are numerous end organ complications of diabetes, the onset of which can be delayed by early diagnosis and treatment. Although assays for diabetes are well founded, tests for its complications lack sufficient specificity and sensitivity to adequately guide these treatment options. In our study, we employed a streptozotocin-induced rat model of diabetes to determine changes in urinary protein profiles that occur during the initial response to the attendant hyperglycemia (e.g. the first two months) with the goal of developing a reliable and reproducible method of analyzing multiple urine samples as well as providing clues to early markers of disease progression. After filtration and buffer exchange, urinary proteins were digested with a specific protease, and the relative amounts of several thousand peptides were compared across rat urine samples representing various times after administration of drug or sham control. Extensive data analysis, including imputation of missing values and normalization of all data was followed by ANOVA analysis to discover peptides that were significantly changing as a function of time, treatment and interaction of the two variables. The data demonstrated significant differences in protein abundance in urine before observable pathophysiological changes occur in this animal model and as function of the measured variables. These included decreases in relative abundance of major urinary protein precursor and increases in pro-alpha collagen, the expression of which is known to be regulated by circulating levels of insulin and/or glucose. Peptides from these proteins represent potential biomarkers, which can be used to stage urogenital complications from diabetes. The expression changes of a pro-alpha 1 collagen peptide was also confirmed via selected reaction monitoring.
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Published date: September 2009
Organisations:
Molecular and Cellular
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Local EPrints ID: 355409
URI: http://eprints.soton.ac.uk/id/eprint/355409
ISSN: 1535-9476
PURE UUID: 74322cb2-c0d4-45fa-8392-55e12a390d3d
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Date deposited: 20 Aug 2013 15:43
Last modified: 15 Mar 2024 03:44
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Author:
Daniela M. Schlatzer
Author:
Jean-Eudes Dazard
Author:
Moyez Dharsee
Author:
Serguei Ilchenko
Author:
Ian Stewart
Author:
George Christ
Author:
Mark R. Chance
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