INSÄNT AV Från läsare DEN 31 :e JANUARI, 1997 vid 23 - tiden
Autoimmunity To Proinsulin Pivotal In IDDM Development
The expression of transgenic proinsulin II
prevents the onset of insulin-dependent diabetes mellitus (IDDM) in nonobese
diabetic mice. Based on that and other findings, Dr. Michelle B. French and
associates at The Walter and Eliza Hall Institute of Medical Research in Victoria,
Australia, conclude that the protective effect is specific for islet pathology.
The researchers explain that insulin and proinsulin could key autoantigens in the
autoimmune destruction of beta-cells that leads to in IDDM in both humans and
nonobese diabetic mice. To evaluate this hypothesis, the Australian scientists
designed an experiment in which ...proinsulin was transgenically expressed in
major histocompatibility complex (MHC) class II bearing cells, including those in
the thymus, to induce tolerance to proinsulin... in nonobese diabetic mice.
Mice that expressed the transgenic proinsulin did not develop either spontaneous or
cyclophosphamide-induced diabetes, whereas ...9 of 10 nontransgenic littermates
became diabetic. And, although isulinitis ...was almost completely absent in
transgenic mice...the degree of sialitis was not statistically different between
transgenic and nontransgenic littermate controls. The finding supports the notion
that transgenic proinsulin expression does not merely induce general
immunosuppression, but rather is ...specifically protective for islet pathology"
Hence, they conclude that proinsulin drives beta-cell autoimmunity.
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