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Mapping the mechanisms behind type 2 diabetes

The islets of Langerhans in the pancreas contain not only insulin-producing cells, but also four other hormone-producing cell types. Using a new method, researchers are to study their interaction by mapping previously unknown genetic networks.
“It will give us new possibilities to direct medicines at new targets”, says associate professor Nils Wierup who will present the first part of the study at EASD in October.

Thanks to access to tissue from deceased organ donors, researchers are able to understand the causes of type 2 diabetes. Tissue from the pancreas contains the islets of Langerhans, which in turn contain beta cells that produce insulin, alpha cells that produce glucagon, and at least three other types of hormone-producing cells (delta cells, PP cells and epsilon cells).

 

Until recently, studies have focused on complete islets. However, using a new method – single cell RNA sequencing – it is now also possible to study each cell type separately and the genes that control how they function.

“If a gene was previously active in one cell type, but inactive in another, the result was neutral. Now we can study every cell type separately and which genes control each one”, says Nils Wierup.

 

In previous studies, Nils Wierup’s research team found there were differences in the classification of the different cell types between people with type 2 diabetes and healthy individuals, and that the gene activity in the different cell types varies among people with type 2 diabetes. Hundreds of genes with previously unknown role in the islets were also found and it was shown that these genes affect each other to varying degrees via different networks.

“We believe that increased knowledge about the effect of the disease on these genetic networks is the key to understanding the causes of the disease progression.”

 

Now they intend to repeat the analyses in an extensive study with considerably more donors and a larger number of cells.

“We will then gain broader as well as more specific knowledge about the differences in cell type composition and which genes are involved in type 2 diabetes in each cell type. This has never been done before”, says Nils Wierup.

 

Then, using the molecular scissors Crispr/Cas9, they will test the effect of the most important gene networks in human cells.

“Most likely our studies will identify new mechanisms that we can affect with medicines”, he concludes.

 

The funding bodies for the research include the Novo Nordic Foundation, Swedish Research Council, Crafoord Foundation, Swedish Diabetes Foundation and Hjelt Foundations.