Science 2 months ago
Discover how defects in primary cilia of pancreatic beta cells may contribute to type 2 diabetes, with new insights on their structure and role in metabolism.

Defects in the tiny cellular structures known as primary cilia in pancreatic beta cells could be a contributing factor to the development of type 2 diabetes (T2D). However, the precise structure and function of these cilia remain largely unexplored. A team of international researchers, led by scientists from the Paul Langerhans Institute Dresden (PLID) at Helmholtz Munich and Technical University of Dresden, used advanced imaging techniques to observe these cilia in their natural state, revealing new insights into their role in beta cell function.

Pancreatic beta cells are responsible for the production of insulin, a hormone crucial for controlling blood glucose levels. When these cells fail to produce enough insulin, it can result in T2D. Recent studies suggest that dysfunctions in the primary cilia of beta cells may be involved in this process. Primary cilia are immobile, hair-like structures found on many cells and are stabilized by protein filaments known as microtubules. These cilia are key in receiving and transmitting signals from the environment, which is essential for proper cell function.

Under the leadership of Dr. Andreas Müller from PLID, the research team utilized cutting-edge imaging methods, including volume electron microscopy (vEM), 3D segmentation, and ultrastructure expansion microscopy (U-ExM), to analyze the three-dimensional structure of primary cilia in beta cells. They examined both human and animal beta cells, providing new information about the way microtubules are organized within the cilia. One significant finding was the discovery that the microtubules in these cilia are not uniform in length, with some ending at varying points inside the cilium, a detail that had not been observed before.

The researchers also explored how these cilia interact with surrounding cells, revealing their crucial role in the signaling networks of the pancreas. The cilia form synapse-like connections with neighboring cells, allowing for the exchange of signals. This communication appears to be vital for coordinating the functions of beta cells with other islet cells, which work together to regulate blood sugar.

In addition to their local functions, the study showed that the primary cilia of beta cells also connect with nervous system cells, suggesting a potential role in neuronal signaling. This could mean that the cilia are not only important for cellular communication within the pancreas but may also contribute to the regulation of metabolism via the nervous system.

These findings highlight the importance of primary cilia in both the function of beta cells and the broader pancreatic signaling network. The research team now plans to delve deeper into the mechanisms and pathways through which these cilia operate, aiming to uncover how their dysfunction could contribute to the development of T2D and to explore new strategies for therapeutic intervention.