Type 1 diabetes: entering the proteomic era

Abstract

During the last decade, a major breakthrough in the field of proteomics has been achieved. This review describes available techniques for proteomic analyses, both gel and non-gel based, particularly concentrating on relative quantification techniques. The principle of the different techniques is discussed, highlighting the advantages and drawbacks of recently available visualization methods in gel-based assays. In addition, recent developments for quantitative analysis in non-gel-based approaches are summarized. This review focuses on applications in Type 1 diabetes. These mainly include proteomic studies on pancreatic islets in animal models and in the human situation. Also discussed are mass spectrometry-based studies on T-cells, and studies on the development of diagnostic markers for diabetic nephropathology by capillary electrophoresis coupled to mass spectrometry. Expert Rev. Proteomics 3(2), 223-236 (2006) From genomics to proteomicsThe term proteome was first introduced in 1994 by Wilkins and coworkers in Siena, Italy [1]. Proteome refers to the already established terms genome and transcriptome, and describes all proteins present in a given cell or organism. Although researchers realized that a systematic analysis of the proteins expressed by a cell or organism would be essential to understand the mechanisms and pathways involved in all aspects of cell growth and differentiation many years earlier, it was only until the completion of the first genome projects that this proteome investigation boosted enormously. This was the start of the post-genomic era, where researchers realized that many processes occur in a cell from the transition from genome to proteome, which could not be explained solely by genomics and transcriptomics.It is undoubtedly clear that the availability of the human genome has aided greatly to our understanding of many genetic disorders and is a great step forward in the diagnosis and treatment possibilities for their associated diseases. However, the majority of diseases, even if they are genetic, are not caused by a single mutation. Rather, they are a combinatorial effect of multiple genetic mutations or an unfavorable combination of common alleles. In addition, environmental factors may also contribute to initiation of the disease, which is true for Type 1 diabetes (T1D). Concurrently with the sequencing of the human genome, RNA-based assays, such as microarrays and the real-time reverse transcriptase PCR technique, were a major research topic, both in fundamental research and in clinical diagnostics [2]. Although our knowledge of the pathways involved in many diseases greatly improved, no information whatsoever could be obtained from these RNA-based studies regarding the importance of translational regulation and the role of post-translational modifications (PTMs). Moreover, some authors proved a very poor correlation between mRNA levels and protein levels [3,4]. From this perspective, proteomics covers the real executing molecules that change expression in a diseased state or aft...

Mitochondria in the pathogenesis of diabetes: a proteomic view

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Hemopexin is up-regulated in plasma from type 1 diabetes mellitus patients: Role of glucose-induced ROS

“…Accordingly, numerous studies have been made to identify biomarkers to monitor the progression of type 1 diabetes mellitus [3,4]. However, most studies have concentrated on genomic profiling approaches as well as animal model-based experiments, with relatively low correlation in response to the clinical prognosis and diagnosis of type 1 diabetes mellitus through human plasma samples [5,6].…”

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells

“…With the recent advances in differential dye labeling and the introduction of the 2D DIGE technique (18) as well as the development of more sophisticated MS equipment for protein identification, an attractive technology for the quantitative analysis of differences in protein profiles has become available (19,20). In the present project we investigated by 2D DIGE analysis the complex processes involved in cytokineinduced ␤-cell death, making use of the rat insulin-producing INS-1E cell line.…”