Novel Experimental Strategies to Prevent the Development of Type 1 Diabetes Mellitus

  • Stellan Sandler
  • Annika K. Andersson
  • Andreea Barbu
  • Claes Hellerström
  • Maria Holstad
  • Ella Karlsson
  • Jan-Olov Sandberg
  • Eva Strandell
  • Johan Saldeen
  • Johnny Sternesjö
  • Linda Tillmar
  • Decio L. Eizirik
  • Malin Flodström
  • Nils Welsh


Type 1 diabetes is an autoimmune disease leading to extensive destruction of the pancreatic β-cells. Our research focusses on the role of β-cells during the course of the disease, aiming at finding novel strategies to enhance β-cell resistance against the cytotoxic damage inflicted by the immune system. Special attention has been paid to the possibility that cytokines released by the immune cells infiltrating the pancreatic islets can directly suppress and kill β-cells. Certain cytokines (interleukin-1β, tumor necrosis factor-α and interferon-γ) either alone or in combination, are able to activate signal transduction pathways in β-cells leading to transcription factor activation and de novo gene expression. In this context, it has been found that induction of inducible nitric oxide synthase mediates an elevated production of nitric oxide, which impairs mitochondrial function and causes DNA damage eventually leading to apoptosis and necrosis. However, other induced proteins SUCH AS heat shock protein 70 and superoxide dismutase may reflect a defense reaction elicited in the β-cells by the cytokines. Our strategy is to further seek for proteins involved in both destruction and protection of β-cells. Based on this knowledge, we plan to apply gene therapeutic approaches to increase expression of protective genes in β-cells. If this is feasible we will then evaluate the function and survival of such modified β-cells in animal models of type 1 diabetes such as the NOD mouse. The long-term goal for this research line is to find novel approaches to influence β-cell resistance in humans at risk of developing type 1 diabetes.


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How to Cite
Sandler S., Andersson A. K., Barbu A., Hellerström C., Holstad M., Karlsson E., Sandberg J.-O., Strandell E., Saldeen J., Sternesjö J., Tillmar L., Eizirik D. L., Flodström M., & Welsh N. (2000). Novel Experimental Strategies to Prevent the Development of Type 1 Diabetes Mellitus. Upsala Journal of Medical Sciences, 105(2), 17-34.
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