Genetic study of insulin-releasing beta-cells presents promise for personalized diabetes treatments

Type 2 diabetes (T2D) affects millions of people worldwide, with many struggling to regulate their blood sugar levels. One of the key factors in this regulation is the function of beta cells in the pancreas, which produce and release insulin—a hormone that helps lower blood sugar. However, scientists still do not fully understand how beta cells respond to elevated glucose levels and why beta cells become dysfunctional in some individuals and not in others.

A new genetics study has now identified a range of new genes and molecular pathways that influence the ability of beta cells to produce and release insulin. These valuable insights could inform the development of new, personalized treatments for T2D.

“A deeper understanding of the β-cell function could lead to more precise disease risk assessments and more effective therapeutic interventions, ultimately improving the quality of life for individuals at risk for or living with diabetes,” says Dr Anne Lundager Madsen, first author of the study, who carried out the research while at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

One-size-fits-all treatments falling short

The study, published in Nature Metabolism, examined the genomes of around 26,000 people and identified 92 different genetic variations that play a role in the function of beta cells and their ability to produce and secrete insulin. Out of the 92 genes, two really stood out: ACSL1 and FAM46C. When the scientists silenced these genes in beta cells, the cells’ ability to release insulin dropped significantly. This makes them promising targets for possible new therapies.

The scientists also found that the genes associated with beta-cell function influenced different molecular pathways of T2D, highlighting the complexity of the relationship between genetics, beta-cell function and T2D.

"Current one-size-fits-all approaches to treating type 2 diabetes are falling short because they fail to account for the complex individualized nature of the disease. Our research underscores that type 2 diabetes arises from a unique mix of genetic and molecular factors in each person. Therefore, the most effective treatments will be those tailored to the individual's specific genetic makeup and beta cell function,” says senior author Professor Torben Hansen from CBMR.

Dr Sílvia Bonàs-Guarch and Professor Jorge Ferrer from the Centre for Genomic Regulation (CRG) at the Barcelona Institute of Science and Technology (BIST) were co-first and co-senior authors of the study, respectively. The study also involved researchers from Aarhus University, Copenhagen University Hospital, Icahn School of Medicine at Mount Sinai, Imperial College London, Lund University, Novo Nordisk Foundation, Rigshospitalet, Steno Diabetes Center Copenhagen, University of Eastern Finland, University of Helsinki, and the Departments of Biology, Clinical Medicine, and Public Health at the University of Copenhagen.

Read the full article in Nature Metabolism: 'Genetic architecture of oral glucose-stimulated insulin release provides biological insights into type 2 diabetes aetiology'