Abstract
Type 2 diabetes mellitus (T2DM) is caused by the failure of the pancreatic beta-cell to secrete sufficient insulin to compensate a decreased response of peripheral tissues to insulin action. The pathological events causing beta-cell dysfunctions are only poorly understood and early markers that would predict islet function are missing. In contrast to immunoassays, unbiased proteomic technologies provide the opportunity to screen for novel marker protein and peptides of T2DM. An important subset of the proteome, peptides and peptide hormones secreted by the pancreas are deregulated in T2DM. The mass range of peptides and small proteins (1-20 kDa) is only sufficiently targeted by peptidomics, a combination of liquid chromatographic and mass spectrometric (MS) peptide analysis. Here, we describe the application of isotope label-free quantitative peptidomics to display and quantify relevant changes in the level of pancreatic peptides and peptide hormones in a preclinical model of T2DM, the Lep ob/Lep ob mouse. The amino acid sequence of statistical relevant top candidates was determined by MS/MS fragmentation or Edman degradation. The comparison of lean versus obese mice revealed increased levels of islet-specific peptides that can be divided into the following categories 1) the major islet peptide hormones insulin, amylin and glucagon; 2) proinsulin and C-peptide and 3) novel processing products of secretogranin, glucagon and amylin. Furthermore, we found increased levels of proteins and peptides implicated in zymogen granule maturation (syncollin) and nutritional digestion. In summary, our findings demonstrate that peptidomics is a valid approach to screen for novel peptide biomarkers.
Keywords: Peptidomics, proteomics, biomarker, diabetes, pancreas, profiling, obesity, insulin, amylin
Combinatorial Chemistry & High Throughput Screening
Title: Peptidomics Biomarker Discovery in Mouse Models of Obesity and Type 2 Diabetes
Volume: 8 Issue: 8
Author(s): Petra Budde, Imke Schulte, Annette Appel, Susanne Neitz, Markus Kellmann, Harald Tammen, Rudiger Hess and Horst Rose
Affiliation:
Keywords: Peptidomics, proteomics, biomarker, diabetes, pancreas, profiling, obesity, insulin, amylin
Abstract: Type 2 diabetes mellitus (T2DM) is caused by the failure of the pancreatic beta-cell to secrete sufficient insulin to compensate a decreased response of peripheral tissues to insulin action. The pathological events causing beta-cell dysfunctions are only poorly understood and early markers that would predict islet function are missing. In contrast to immunoassays, unbiased proteomic technologies provide the opportunity to screen for novel marker protein and peptides of T2DM. An important subset of the proteome, peptides and peptide hormones secreted by the pancreas are deregulated in T2DM. The mass range of peptides and small proteins (1-20 kDa) is only sufficiently targeted by peptidomics, a combination of liquid chromatographic and mass spectrometric (MS) peptide analysis. Here, we describe the application of isotope label-free quantitative peptidomics to display and quantify relevant changes in the level of pancreatic peptides and peptide hormones in a preclinical model of T2DM, the Lep ob/Lep ob mouse. The amino acid sequence of statistical relevant top candidates was determined by MS/MS fragmentation or Edman degradation. The comparison of lean versus obese mice revealed increased levels of islet-specific peptides that can be divided into the following categories 1) the major islet peptide hormones insulin, amylin and glucagon; 2) proinsulin and C-peptide and 3) novel processing products of secretogranin, glucagon and amylin. Furthermore, we found increased levels of proteins and peptides implicated in zymogen granule maturation (syncollin) and nutritional digestion. In summary, our findings demonstrate that peptidomics is a valid approach to screen for novel peptide biomarkers.
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Cite this article as:
Budde Petra, Schulte Imke, Appel Annette, Neitz Susanne, Kellmann Markus, Tammen Harald, Hess Rudiger and Rose Horst, Peptidomics Biomarker Discovery in Mouse Models of Obesity and Type 2 Diabetes, Combinatorial Chemistry & High Throughput Screening 2005; 8 (8) . https://dx.doi.org/10.2174/138620705774962535
DOI https://dx.doi.org/10.2174/138620705774962535 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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