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 are 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 U.S., 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 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.
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 end at different distances within the cilium. This was demonstrated for the first time in the cilia of beta 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.
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 says.
In order to better understand how the primary cilia are involved in T2D pathogenesis, the researchers want to further investigate the mechanisms and pathways.
More information:
Andreas Müller et al, Structure, interaction and nervous connectivity of beta cell primary cilia, Nature Communications (2024). DOI: 10.1038/s41467-024-53348-5
Provided by
Deutsches Zentrum fuer Diabetesforschung DZD
Citation:
Beta cells: New insights into the structure, interactions and neuronal networking of primary cilia (2024, November 4)
