Whole organ 3D imaging reveals remaining insulin producing cells in type 1 diabetes

Three‑dimensional images of entire human pancreases in which the islets of Langerhans are stained for insulin (red). Despite the marked difference between the pancreas from the non‑diabetic and the type 1 diabetic donor, the latter still contained hundreds of thousands of insulin‑producing cells.

ImageUlf Ahlgren

“Our results suggest the pancreas can retain β cells – those insulin‑producing cells that are typically destroyed in type 1 diabetes – in a way that has not previously been recognized,” says Ulf Ahlgren, Professor at the Department of Medical and Translational Biology at Umeå University.

Using advanced imaging technologies, researchers at Umeå University have created the first complete 3D map of an entire pancreas from a donor with late‑onset type 1 diabetes, at a microscopic resolution. The analysis revealed that while traditional islets of Langerhans were largely depleted of β-cells, a substantial number of insulin‑producing cells still remained outside the islet structures. These were primarily found as individual cells or as small clusters of b-cells, in which the cells were distanced from all other endocrine cell types. In total, the researchers identified hundreds of thousands of insulin‑positive objects.

“The fact that these cells are located outside the islets and are more numerous than the islet‑associated β-cells, i.e. in inversed proportions compared to non-diabetic subjects, suggests that they may either be more resistant to destruction or that new β-cells can be formed,” says Ulf Ahlgren.

The researchers argue that analyses traditional islet-focused analyses risk underestimating how many β-cells actually survive in type 1 diabetes. The new findings point to a previously overlooked cellular reservoir that could, in the long term, become a target for novel therapeutic strategies.

“The ability to study individual cells throughout an entire organ and from all angles has the potential to change how we think about β‑cell loss,” explains Ulf Ahlgren. “If certain regions of the pancreas promote β‑cell survival, understanding these microenvironments could help guide the development of therapies that stabilize, or even expand the remaining b-cells in type 1 diabetes.”

Doctoral student Joakim Lehrstrand also emphasizes the importance of broadening the perspective.

“This work shows that we must look beyond the islets when studying β‑cell biology in type 1 diabetes,” he says.

PhD student Joakim Lehrstrand (foreground) and Professor Ulf Ahlgren at a so‑called light sheet fluorescence microscopy, one of the techniques they use to create three-dimensional images of the pancreas in diabetes. 

ImageBjörn Morén

The research group believes that whole‑organ 3D imaging will become a key tool in future studies of type 1 diabetes and other pancreas related diseases, such as type 2 diabetes and pancreas cancer. The method makes it possible to identify specific regions or even individual cells throughout the entire organ, something that has previously been extremely difficult using conventional techniques. These regions can then be isolated for further molecular analyses.

“Hopefully, this will help us understand whether and how β-cells and their microenvironment differ within the pancreas in diabetes,” says Ulf Ahlgren.

The results have been published in Science Advances.