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Malfunctions of tiny cell extensions (primary cilia*) in the beta cells of the pancreas may be a cause of type 2 diabetes. Little is known about the structure and function of these cilia. An international research team led by scientists from the Paul Langerhans Institute Dresden (PLID) at the German Center for Diabetes Research (DZD) and Helmholtz Munich at the University Hospital Carl Gustav Carus of the Technical University of Dresden has used various new imaging techniques to visualize primary cilia in their natural environment. Their research not only provides detailed insights into the structure of these cilia but also reveals 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 essential for the uptake of glucose from the bloodstream. Various factors can impair the ability of these cells to produce insulin, potentially leading to the development of type 2 diabetes (T2D). Recent studies suggest that dysfunction of the primary cilia in beta cells may also be a contributing factor to T2D.
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Subscribe for FREEMost cells in our body have immobile primary cilia. These small extensions are stabilized by a framework of tubular protein rods called microtubules. Cilia help cells receive and transmit external signals. An international team from PLID, a partner of Helmholtz Munich and the DZD, Human Technopole in Italy, the Janelia Research Campus, and Yale University in the USA, investigated the structure and function of primary cilia in beta cells. Led by Dr. Andreas Müller, a senior scientist at PLID (Director: Prof. Michele Solimena) and the study’s first author, the researchers used imaging techniques such as volume electron microscopy (vEM), 3D segmentation, and ultrastructural expansion microscopy (U-ExM) to visualize the three-dimensional shape of primary cilia in beta cells within their natural environment.
Unique Structural Characteristics
The primary cilia observed in this study came from both animal and human beta cells. The researchers examined how the skeletal structure (axoneme) formed by microtubules is organized. They discovered structural features of stabilizing cilia with microtubules ending at different points within the cilium, a characteristic shown for the first time in beta cell cilia.
Role in Signal Transmission Between Beta Cells and Islet Cells
The researchers also examined how cilia interact with neighboring cells to infer their signaling functions. They found that primary cilia closely communicate with surrounding cells and their cilia, playing a key role in signal transmission and networking between beta cells and other islet cells. They form synapse-like structures that connect adjacent cells.
Interactions with Nerve Tissue Cells
Further analysis of the imaging data suggested that the primary cilia of beta cells also interact with nerve tissue cells, which could indicate a role in neuronal signal transmission.
"The structural data from this study highlight the importance of primary cilia in beta cells as crucial junctions for islet cell function," summarizes Müller.
To better understand how primary cilia are involved in T2D pathogenesis, the researchers plan to further investigate the underlying mechanisms and pathways. This research is also supported by the DZD Young Talent Program.
Reference: Müller A, Klena N, Pang S, et al. Structure, interaction and nervous connectivity of beta cell primary cilia. Nat Commun. 2024;15(1):9168. doi: 10.1038/s41467-024-53348-5
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