Unraveling the Pathogenesis of Type 1 Diabetes with Proteomics: Present And Future Directions
Type 1 diabetes (T1D) is the result of selective destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans. T1D is due to a complex interplay between the β-cell, the immune system, and the environment in genetically susceptible individuals. The initiating mechanism(s) beh...
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Published in | Molecular & cellular proteomics Vol. 4; no. 4; pp. 441 - 457 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
01.04.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Type 1 diabetes (T1D) is the result of selective destruction of the insulin-producing β-cells in the pancreatic islets of
Langerhans. T1D is due to a complex interplay between the β-cell, the immune system, and the environment in genetically susceptible
individuals. The initiating mechanism(s) behind the development of T1D are largely unknown, and no genes or proteins are specific
for most T1D cases. Different pro-apoptotic cytokines, IL-1 β in particular, are present in the islets during β-cell destruction
and are able to modulate β-cell function and induce β-cell death. In β-cells exposed to IL-1 β, a race between destructive
and protective events are initiated and in susceptible individuals the deleterious events prevail. Proteins are involved in
most cellular processes, and it is thus expected that their cumulative expression profile reflects the specific activity of
cells. Proteomics may be useful in describing the protein expression profile and thus the diabetic phenotype. Relatively few
studies using proteomics technologies to investigate the T1D pathogenesis have been published to date despite the defined
target organ, the β-cell. Proteomics has been applied in studies of differentiating β-cells, cytokine exposed islets, dietary
manipulated islets, and in transplanted islets. Although that the studies have revealed a complex and detailed picture of
the protein expression profiles many functional implications remain to be answered. In conclusion, a rather detailed picture
of protein expression in β-cell lines, islets, and transplanted islets both in vitro and in vivo have been described. The data indicate that the β-cell is an active participant in its own destruction during diabetes development.
No single protein alone seems to be responsible for the development of diabetes. Rather the cumulative pattern of changes
seems to be what favors a transition from dynamic stability in the unperturbed β-cell to dynamic instability and eventually
to β-cell destruction. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 1535-9476 1535-9484 |
DOI: | 10.1074/mcp.R500002-MCP200 |