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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Novel Oral Anticoagulants in Peripheral Arterial and Coronary Artery Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Design, Synthesis and In-vivo Hypoglycemic Evaluation of Novel Non - TZD’S in a Type - 2 Diabetic Model
Medicinal Chemistry Impaired Glycogen Synthase Activity and Mitochondrial Dysfunction in Skeletal Muscle: Markers or Mediators of Insulin Resistance in Type 2 Diabetes?
Current Diabetes Reviews Vitamins and Cognition: A Nutrigenomics Perspective
Current Nutrition & Food Science The Ascent of Mineralocorticoid Receptor Antagonists in Diabetic Nephropathy
Current Clinical Pharmacology Atypical Presentation Of Anti-Retroviral Therapy Induced Lactic Acidosis as Acute Right Ventricular Failure And Severe Pulmonary Hypertension
New Emirates Medical Journal Flavonoid Enriched Fraction of Campylandra aurantiaca Attenuates Carbon Tetrachloride Induced Oxidative DNA Damage in Mouse Peritoneal Macrophages in Animal Model
Current Drug Discovery Technologies Large Artery Stiffness and Antihypertensive Agents
Current Pharmaceutical Design Podocytes as Target of Vitamin D
Current Diabetes Reviews Vitamin D and Asthma: Scientific Promise and Clinical Reality
Current Respiratory Medicine Reviews Evaluating Drug Safety in Children and Adolescents with Bipolar Disorder
Current Drug Safety Vaccination Against High Blood Pressure
Current Pharmaceutical Design Potential Natural Dual Agonist PPARα/γ-induced Antidiabetic and Antidyslipidemic Properties of Safrole-Free Nutmeg Seed (Myristica fragrans Houtt) Extract
The Natural Products Journal Phenylbutyric Acid: Simple Structure - Multiple Effects
Current Pharmaceutical Design Editorial (Thematic Issue: Therapeutic Applications of Advanced Drug Delivery Systems)
Current Pharmaceutical Design Long-Acting Antipsychotic Medications
Current Drug Targets Unsafe Abortion: The Silent Endemic; An Avoidable Cause of Maternal Mortality. A Review
Current Women`s Health Reviews Circulating Levels of Uric Acid and Risk for Metabolic Syndrome
Current Diabetes Reviews The Need for Physiologically Relevant Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) Ligands
Endocrine, Metabolic & Immune Disorders - Drug Targets Pharmacogenetics of the Metabolic Disturbances and Atherosclerosis Associated with Antiretroviral Therapy in HIV-Infected Patients
Current Pharmaceutical Design