​Vision and research questions

The goal is to prevent type 1 diabetes.​

The primary goal in the diabetes group is to understand the pathogenesis of the complex autoimmune disease type 1 diabetes. We focus on the immune system, and work on understanding how intrinsic and extrinsic factors such as dietary gluten contributes to the disease.

Main findings

Main projects

Glycosphingolipids

Glycosphingolipids are supposed to play an important role in the metabolism and function of the beta cells. In many ways, beta cells resemble neural cells. This is supported by novel findings that co-transplantation of human pancreatic islets with neural stem cells increases beta-cell proliferation and vascular regrowth. Also, during the foetal development of beta cells, stem cells from neural ectoderm are found in situ at the beta cells. Supposedly these neural cells somehow influence the beta cells. Very likely, this could also be the case regarding sphingolipids including sulfatide; these compounds are intensively present in the myelin tissue surrounding the nerves, having the function of facilitating electric impulses. In beta cells, especially sulfatide is important. It facilitates folding of proinsulin and insulin. Also, at low pH sulfatide preserves the insulin crystals. Sulfatide facilitates exocytosis and afterwards opens the potassium channels so that the individual beta cells can rest to build up new secretory granules close to the cell membrane, meanwhile other beta cells take over the secretory responsibilities. Furthermore, sulfatide inhibits cytokine secretion, it is antagonistic to TLR4, and it facilitates NKT cells after presentation by CD1 molecules. 

Pesticides and chemicals

The development of T1D is influenced by environmental factors, but only some have been identified. The increase in the incidence of T1D over the last half century has paralleled an increasing usage of pesticides, suggesting that these chemicals could be of pathogenic importance during disease development.

We have studied the effect of common pesticides and combinations hereof on secretion and viability of beta- and non-beta cell lines and found great variability in the toxicity of the products. Both stimulatory and inhibitory effects were seen, depending on concentration and chemical.

The study of pesticides is complicated by the fact that most pesticides is degraded in the nature into one or several compounds that might have other biological effects than the original product.

Beta-cell activity

In type 1 diabetes, the insulin-producing cells are destroyed because the immune system is incorrectly directed at the cells that are destroyed. A number of observations have shown that the insulin-producing cells are attacked more frequently when they are active than when they are at rest, including that glucose increases the expression of known beta cell antigens, beta cell activity is associated with the development of diabetes, T1DM can be prevented in animals by reducing beta cell activity, immune response can be down-regulated specifically and that treatment is effective in animal models. Studies of activity-induced antigens have the potential to develop immunomodulatory therapy, however, the prospects for the treatment of T1DM in humans are unclear. On the one hand, early trials have not yielded the desired result, and on the other hand, T-effector cells in T1DM patients have recently been found unaffected by inhibitory regulatory T-cells.

Group Leader

Karsten Buschard

Professor, overlæge, dr.med., dr.med.vet.

CV, Karsten ​

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Group​ members