They discover how a rare type of tumor forms in the beta cells of the pancreas

Insulinomas are rare tumors that involve an overgrowth of beta cells, which are responsible for secreting insulin. They are often diagnosed because they cause excessive insulin production, which often leads to hypoglycemia. Each year, four out of every million people are diagnosed with insulinomas and, in most cases, they are benign. If they are detected early and removed with surgery, they have a good prognosis and only one in ten cases of insulinomas are malignant.

An experimental study led by Pompeu Fabra University (UPF) in Barcelona describes the mechanism by which insulinomas are formed.

The team that carried out the study included, among others, Mireia Ramos and Lorenzo Pasquali, from the UPF.

According to the study, insulinomas arise from the accumulation of rare mutations that lead to a homogeneous change in the epigenetic profile of pancreatic beta cells. This change in profile causes beta cells to express unusually high levels of oncogenes, growth and transcription factors, and genes related to insulin production.

These mutations vary among the 42 insulinomas analysed and, for the most part, accumulate in regulatory regions of the genome. “The uniqueness of insulinomas is that all of them, whatever mutations they have, end up acquiring the same epigenetic profile,” adds Lorenzo Pasquali, director of the Endocrine Regulatory Genomics Group at UPF, who led the research.

This new epigenetic profile causes tumor beta cells to lose their repression marks and, unlike healthy beta cells, to have a series of oncogenes, growth and transcription factors, and genes related to insulin production active, which alter their function.

Apart from insulinomas, pancreatic beta cells are also implicated in other debilitating diseases such as diabetes mellitus. For this reason, “we are particularly interested in understanding how these cells lose control, disrupt the expression of the genes that make them function normally and end up altering insulin secretion,” says Pasquali.

Detail of insulinoma cells expressing insulin (red). (Photo: UPF)

The group is now working to better understand the mechanism by which beta cell overgrowth occurs, which could have therapeutic implications in the future for the treatment of other diseases in which beta cells are altered.

The San Raffaele Hospital Scientific Institute in Milan, Italy, the University of Colorado at Boulder (USA), the University of Barcelona, ​​the Bellvitge Biomedical Research Institute (IDIBELL) in Hospitalet de Llobregat, the Parc Taulí Research and Innovation Institute (I3PT) in Sabadell, the Barcelona Biomedical Research Institute (IRB Barcelona) and the Biomedical Research Network Centre for Diabetes and Associated Metabolic Diseases (CIBERDEM) in Spain also participated in this study.

The study is entitled “Implications of noncoding regulatory functions in the development of insulinomas”. It has been published in the academic journal Cell Genomics. (Source: Pompeu Fabra University)