Proteome analysis -- A novel approach to understand the pathogenesis of Type 1 diabetes mellitus

Article type: Research Article

Authors: Karlsen, Allan E. | Sparre, Thomas | Nielsen, Karin | Nerup, Jørn | Pociot, Flemming

Affiliations: Steno Diabetes Center, Gentofte, Denmark

Note: [] Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark. Fax: +45 4443 7313; E-mail: [email protected]

Abstract: Type 1 (insulin-dependent) diabetes mellitus (T1DM) is associated with a specific destruction of the insulin-producing beta-cells in the islets of Langerhans. Several factors, e.g. genetic, environmental and immunologial, may be involved in the etiology and pathogenesis of T1DM. Autoreactive T- and B-lymphocytes, together with macrophages infiltrate the islets during the pathogenesis, releasing a mixture of cytokines, demonstrated to be specifically toxic to the beta-cells within the islets. Our goal is to understand the molecular mechanisms responsible for the beta-cell specific toxicity enabling us to design novel intervention strategies in T1DM. The proteome approach allows us to get a detailed picture of the beta-cell proteins, which change expression level or are post-translationally modified in different {\it in vitro} and {\it in vivo} models of T1DM-associated beta-cell destruction. Combining the information obtained from this extended proteome approach, with that of genetic-, transcriptome- and candidate-gene approaches, we believe that it is possible to reach this goal.

Journal: Disease Markers, vol. 17, no. 4, pp. 205-216, 2001