Proteome analysis--a novel approach to understand the pathogenesis of Type 1 diabetes mellitus.
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 in vitro and 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.
Karlsen
A E
AE
Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark.
Sparre
T
T
Nielsen
K
K
Nerup
J
J
Pociot
F
F
D016922:Cellular Senescence / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D020543:Proteome
D007375:Interleukin-1; D020543:Proteome