Dysfunctions of the tiny cell processes (primary cilia*) of the pancreatic beta cells could be a cause of type 2 diabetes. Little is known about the structure and function of these cilia. An international research team led by DZD researchers from the Paul Langerhans Institute Dresden (PLID) at Helmholtz Munich of the Faculty of Medicine of the Technical University of Dresden has used various new imaging techniques to visualize the primary cilia in their natural environment. Their investigations not only provide detailed insights into the structure of these cilia, but also show their connection to the nervous system. The results have now been published in 'Nature Communications'.

The beta cells of the pancreas are responsible for releasing the hormone insulin, which is vital for the absorption of glucose from the bloodstream. Various factors can impair the ability of these cells to produce insulin. This can lead to the development of type 2 diabetes (T2D). Current studies indicate that dysfunctions of the primary cilia of the beta cells may also be a cause of T2D.

Most cells in our body have immobile primary cilia. These small projections are stabilized by a kind of scaffold made of tubular protein rods, the microtubules. The cilia help the cells to receive and transmit signals from the outside. An international team from PLID, a partner of the German Center for Diabetes Research (DZD), the Human Technopole in Italy, the Janelia Research Campus and Yale University in the USA, investigated the structure of the primary cilia of beta cells as well as their function. Under the direction of Dr. Andreas Müller, scientist in the Department of Molecular Diabetology at the PLID (Director: Prof. Michele Solimena) and first author of the study, imaging techniques such as volume electron microscopy (vEM), 3D segmentation and ultrastructure expansion microscopy (U-ExM) were used to visualize the three-dimensional shape of the primary cilia of beta cells in their natural environment.
 

Beta cell with cilia. © Andreas Müller, PLID

Special design of the skeletal structure

The primary cilia observed in this study originated from both animal and human beta cells. The researchers investigated how the skeletal structure (axoneme) formed from microtubules is organized. They discovered structural features of stabilizing cilia with microtubules that ended at different distances within the cilium. This was demonstrated for the first time in the cilia of beta cells. 

Role in signal transmission between beta cells and other islet cells

The researchers also examined how the cilia interact with neighboring cells in order to draw conclusions about their signaling functions. They found that the primary cilia exchange information closely with surrounding cells and their cilia and play an important role in the signal transmission and networking of beta cells with other islet cells. They form synapse-like structures that pinch neighboring cells.

Interactions with cells of the nervous tissue

Further analyses of the image data indicated that the primary cilia of the beta cells also interact with cells of the nervous tissue. This could indicate a role in neuronal signal transmission.

“The structural data of this study show the importance of the primary cilia of beta cells as important junctions for islet cell function,” Müller summarizes the results.

In order to better understand how the primary cilia are involved in T2D pathogenesis, the researchers want to further investigate the mechanisms and pathways. This research is supported by the DZD Young Talent Program.

*Primary cilia
Primary cilia are small, sensory structures that occur in many cell types. They act like small antennas that perceive signals from the environment and transmit them to the inside of the cell.  These small projections are stabilized by a kind of scaffold made of tubular protein rods, the microtubules. In the beta cells of the pancreas, primary cilia play a role in communication between cells and are associated with diabetes.

Original publication:
Andreas Müller... Michele Solimena. Structure, interaction, and nervous connectivity of beta cell primary cilia. Nat Commun 15, 9168 (2024). https://doi.org/10.1038/s41467-024-53348-5

The Technische Universität Dresden (TU Dresden) is one of Germany's niversities of Excellence, esteemed for its exceptional standards in research and teaching spanning diverse fields. The Faculty of Medicine at TU Dresden is dedicated to propelling medical science and healthcare forward through interdisciplinary collaboration and pioneering research. https://www.uniklinikum-dresden.de/en

The Paul Langerhans Institute of Helmholtz Munich at the University Hospital Carl Gustav Carus and the Faculty of Medicine at TU Dresden (PLID) contributes decisively to a better understanding of the mechanisms of the disease and to explore new therapeutic options. The institute is a founding-partner of the German Center for Diabetes Research (DZD e.V.) and has been a satellite institute of Helmholtz Munich since January 2015. Its program comprises research into the pathophysiology of type 1 and type 2 diabetes mellitus. The main focus is on the mechanisms which cause the destruction and/or limited function of pancreatic beta cells and insufficient insulin secretion. In addition, the PLID also plays an outstanding role as only German transplant center for human pancreatic islet cells. https://tu-dresden.de/med/mf/plid

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Munich – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en