The gene Wnt4 becomes active after sensing β cells

Diabetes affects millions of people worldwide and occurs
when the body does not produce enough insulin (a hormone that maintains healthy blood sugar), or when the body cannot use the insulin it produces efficiently.
When the number of β cells is too low or they don't work properly, not enough insulin is released
.
β cells communicate with each other to secrete insulin
in a coordinated manner.
An international team of scientists from the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Paul Langhhans Institute in Dresden (PLID), the University of Oulu in Finland and the University of Copenhagen in Denmark have now shown that the Wnt4 gene in β cells enables them to sense glucose and release insulin hormones, which allow other cells in the body to store glucose
.
These insights may help create alternative β cells
for diabetes treatment in the future.

At birth, babies begin to eat food and convert food into energy
.
Many nutrients can be converted into sugar (glucose) and released into the bloodstream
.
Higher blood sugar levels signal the β cells in the pancreas to release insulin, which allows blood sugar to enter the cells for use or storage
as energy.
However, at different stages of life, food-sensing β cells need to adapt to different foods and needs
.
In a recent study by Nature Communications Anne Grapin-Botton, director of MPI-CBG, she and her team in Dresden and the team at the Novo Nordisk Foundation Center for Stem Cell Biology in Copenhagen, Denmark, and colleagues from Carl Gustav Carus from the Technical College of Dresden found that the gene Wnt4 becomes active in food-sensing β cells as they mature
in life early after birth.

 

The discovery of how it all started began at
Harvard in the '90s, when then-postdoctoral researcher Anne Grapin-Botton had a discussion
with Seppo Vainio, now head of the research department at the University of Oulu 。 Seppo Vainio said: "I remember when I studied Wnt4 during kidney development, we speculated that this signal would also play a role
in the development of the pancreas.
" But researchers lacked the right tools
at the time.
More than 20 years later, Keiichi Katsumoto, a postdoctoral researcher in Anne Grapin-Botton's lab, was keen to figure out the role
of the Wnt4 gene in pancreatic development.
Meanwhile, Vainio's lab in Oulu further developed their mouse model: "With all these tools, we can target the function of Wnt4 in pancreatic development and physiology in Anne Grapin-Botton's research lab," says
Seppo Vainio.

Keiichi Katsumoto describes what he observed: "We found that during cell maturation, the gene Wnt4 is expressed
in β cells.
Cells that begin to express Wnt4 stop proliferating and become more functional
.
We found that the less Wnt4, the less
insulin β cells secrete.
The team found that although β cells were able to detect sugar in the blood, they secreted less
insulin in response to glucose.

"When we saw mice without the Wnt4 gene developing diabetes, we knew we had found something important, but we didn't know how it worked," said
Anne Grapin-Botton, who oversaw the study.
"We know from studies of other organs, especially our collaborator Seppo Vainio and his colleagues, that this gene is the signal
that cells send to other cells.
Excitingly, we discovered the communication between β cells in the pancreas, its preservation between several animal species, and the mechanisms by which it operates, especially the profound metabolic changes
it triggers in β cells.
However, it is not clear whether β cells are constantly releasing Wnt4 or under special circumstances
.
This will be something
we want to explore in the future.
”

Katsumoto said: "The results also showed that the increase in Wnt4 made β cells mature
shortly after birth.
" Our next step is to understand why Wnt4 is expressed
as cells mature.
"These results may support replacing diabetes treatment
with β cells that promote maturation with the addition of Wnt4.
"