Beta Cell Gene Linked to Insulin Production

Researchers from Germany, Denmark and Finland have identified a gene that plays a role in the secretion of blood sugar-regulating hormone insulin. The findings could lead to improved treatments for diabetes, a disease that affects millions of people worldwide and develops when the body either generates insufficient amounts of insulin or cannot effectively use the insulin it produces.

Higher blood sugar levels signal beta cells in the pancreas to release insulin, which lets the blood sugar into the cells to use or store it as energy. However, at different stages of life, the food-sensing beta cells need to adapt to different foods and needs.

The current study—undertaken by researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany; the Paul Langerhans Institute Dresden (PLID); and the Universities of Oulu, Finland and Copenhagen, Denmark—found that the gene Wnt4 enables beta cells to sense glucose and release insulin, enabling other cells in the body to store glucose. They also found that the gene becomes active in food-sensing beta cells as they mature in early postnatal life.

“We found that the gene Wnt4 is expressed in beta cells during the maturation of the cell,” says Keiichi Katsumoto, a postdoctoral researcher in the lab of Anne Grapin-Botton, director at MPI-CBG. “The cells that start expressing Wnt4 stop proliferating and become more functional. We saw that with less Wnt4, the beta cell secretes less insulin.”

Even though the beta cells were able to detect sugar in the blood, they secreted less insulin in response to glucose. “When we saw that mice without the gene Wnt4 were becoming diabetic, we knew we had found something important, but we did not understand how it was acting,” says Grapin-Botton. “We understood from work in other organs, notably our collaborator Seppo Vainio [a research unit leader at the University of Oulu] and his colleagues, that this gene is a signal sent by cells to others. It was exciting to find communication between beta cells in the pancreas, its conservation across several animal species and the mechanisms by which it operates, notably the profound metabolic changes it provokes in beta cells. However, we do not understand yet if beta cells release Wnt4 constantly or under special circumstances. This will be something, we want to explore in the future.”

Katsumoto adds that the results also suggest that the increase of Wnt4 shortly after birth enables beta cells to mature. “The next step is to understand why Wnt4 becomes expressed as the cells mature” to support the development of replacement beta cells for diabetes therapy with added Wnt4 to promote maturation, Katsumoto adds.

The findings  were published recently in Nature Communications.