By Elodie Vaz | Published on May 8,
2026 | 4 min read
Type 2 diabetes is
characterized by chronically elevated blood glucose levels resulting from an
imbalance between two essential pancreatic hormones: insulin, secreted by beta
cells, and glucagon, produced by alpha cells. When insulin production or action
declines, or when glucagon production becomes excessive, glucose homeostasis is
disrupted. While the genetic foundations of the disease are well documented,
the mechanisms regulating gene expression in these cells remain only partially
understood. The epigenome—a collection of chemical modifications to DNA that
influence gene activity without altering its sequence—is now emerging as a
central regulator of these processes.
To gain a better understanding,
a team from Lund University set out to establish the most detailed epigenomic
map to date of the cells involved in blood glucose regulation. Their objective
was to understand how epigenetic profiles control gene expression in beta and
alpha cells, and to determine how these profiles are altered in type 2
diabetes.
Behind the scenes of
the cells controlling blood sugar
The researchers analyzed
hundreds of thousands of pancreatic cells obtained from 24 individuals, both
diabetic and non-diabetic. This large-scale approach made it possible to
identify epigenetic signatures specific to each cell type. The study, published
on April 24 in Nature Metabolism, focused particularly on DNA
methylation, a key mechanism in transcriptional regulation.
To test the functional
role of these modifications, the scientists manipulated methylation near the
genes encoding insulin and glucagon in cultured beta cells, thereby assessing
its direct impact on hormone expression.
The findings show that
many genes essential to hormone production are regulated by variations in
methylation. “This study made it possible, for the first time, to describe in
detail epigenetic profiles specific to each cell type. It shows that many genes
essential for insulin and glucagon production are regulated by differences in
DNA methylation,” explained lead author Charlotte Ling in a press release.
The researchers also
identified marked alterations in diabetic patients. Among them, the epigenetic
overexpression of the transcription factor ONECUT2 in beta cells appeared
particularly significant. This abnormality disrupts cellular energy production
and insulin secretion, potentially contributing to disease progression.
“Here, for the first
time, we precisely show which regions regulate insulin and glucagon production
through DNA methylation, giving us the opportunity to develop future
epigenetics-based treatments,” emphasized Charlotte Ling. “This allows us to
better understand why beta cells lose their function in diabetes. In the longer
term, this knowledge could help us identify new personalized therapeutic
targets,” she added.
What if damaged cells
could be repaired?
This mapping represents a
major advance in understanding the molecular mechanisms underlying type 2
diabetes. It highlights the dynamic role of the epigenome in both the function
of pancreatic endocrine cells and their pathological alterations.
“We are now trying to
understand which of these modifications are reversible and whether this could
help beta cells recover their function in people with diabetes. A key issue is
determining whether the effects of modifying DNA methylation persist in the
cell over time,” explained Charlotte Ling.
Ultimately, this research
opens the door to targeted therapeutic strategies capable of specifically
modulating the epigenome. Such an approach could transform diabetes management
by moving toward precision medicine based on cellular reprogramming.
Read next: Type
1 Diabetes: “Cyborg” transplants to restore the pancreas
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on
human life. A registered nurse since 2010, she spent twelve years at patients’
bedsides before exchanging her stethoscope for a notebook. She now investigates
the links between environment and health, convinced that the vitality of life
cannot be reduced to that of humans.
