Researchers at Sweden’s Lund University have conducted the most detailed mapping to date of the epigenome of cells that regulate the body’s blood sugar levels. This research natural metabolismshows how chemical changes to DNA affect both insulin-producing beta cells and glucagon-producing alpha cells, and how these patterns change in type 2 diabetes.
All cells in the body have the same set of genes, but use different genes to develop into different types of cells. The epigenome controls this process by activating and deactivating cell type-specific genes. Insulin and glucagon, the hormones that regulate blood sugar, are produced by cells in the pancreas. Insulin, which lowers blood sugar levels, is produced in the beta cells of the pancreas, and glucagon, which raises blood sugar levels, is produced in the alpha cells. An imbalance between the two hormones increases the risk of high blood sugar levels and, in the long term, type 2 diabetes.
By analyzing hundreds of thousands of such cells from 24 people with and without diabetes, the Lund researchers were able to map how epigenetic patterns control gene activity within cells, and how this changes in diabetes. The results show how epigenetic changes affect cells that regulate blood sugar, and how these changes differ between people with type 2 diabetes and those without. This mapping study is the first of its kind.
This made it possible for the first time to describe detailed cell-specific epigenetic patterns. This study shows that many genes central to insulin and glucagon production are regulated by differential DNA methylation. ”
Charlotte Ring, Professor of Epigenetics at Lund University and lead author of the study
DNA methylation is an epigenetic process that attaches small chemical groups to DNA to control how a cell’s genes are used, without changing the actual DNA sequence. To see if they could affect genes in insulin-producing cells themselves, the researchers changed DNA methylation near the genes for insulin and glucagon. This part of the study was performed in cultured beta cells.
“Now, for the first time, we have shown precisely which regions regulate insulin and glucagon production through DNA methylation. This provides an opportunity to develop future treatments based on epigenetics,” says Charlotte Lin.
A particularly important finding in this study concerned specific transcription factors, proteins that tell cells which genes to use and in what amounts. The transcription factor ONECUT2 was found to be epigenetically elevated in beta cells of patients with type 2 diabetes. Elevated levels of ONECUT2 impair the energy production and insulin release capacity of beta cells, and this mechanism may contribute to disease development.
“This provides a deeper understanding of why beta cells lose function in diabetes. In the long term, this knowledge may help identify new personalized treatment targets,” says Charlotte Lin.
Some control over epigenetic changes could pave the way for future treatments that target cell types affected by diabetes.
“We now want to understand which of these changes can actually be reversed and whether this can help restore beta cell function in diabetes. The key is to see whether the effects of DNA methylation editing can be sustained in the cell over a long period of time,” says Charlotte Lin.
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Reference magazines:
Ohori, JK, Others. (2026). Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes. natural metabolism. DOI: 10.1038/s42255-026-01498-9. https://www.nature.com/articles/s42255-026-01498-9
