Cells chat via cannabinoids, about your future diabetes

"Our discovery is essential to understand the mechanisms responsible for the development of type 2 diabetes, which occurs generally in adults and is often associated with weight gain. If our further research brings expected results, perhaps in the near future we will be able to use them to free up at least some patients from the nightmare of continuous insulin injections," says Prof. Agnieszka Dobrzyn from the Nencki Institute.

In the latest publication in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers from the Nencki Institute showed that the pathway of chemical signals involving cannabinoids not only plays an important role in communication between alpha and beta cells, but also is involved in keeping the identity of the latter. Cannabinoids produced by the alpha cells may in fact activate cannabinoid CB1 receptors located in the pancreatic islets. These receptors determine the differentiation of cell function and may increase the ability to produce insulin in response to glucose by beta cells.

"Observing the changes in the architecture of islets during embryonic development in mice and in pseudoislets -- a model we generated in our lab -- was also very interesting. Depending on the concentration of cannabinoids and the activity of two different receptors, the islets became larger or smaller, while the alpha cells, usually located outside the islets, were able to migrate inside," explains Dr. Katarzyna Malenczyk fom the Nencki Institute, the first author of the publication.

The studies already have their practical application. They suggest that future mothers consuming substances containing cannabinoids in the pregnancy period are more likely to deliver children with impaired pancreatic islet architecture, and therefore prone to type 2 diabetes.

"Under no circumstances should it be concluded from our work that consumption of marijuana can be a way to cure diabetes," Prof. Dobrzyn warns and explains: "The concentration of glucose in the blood is determined by the balance between the activities of alpha and beta cells of the pancreas and insulin target tissues such as skeletal muscle and adipose tissue. In adults, more cannabinoids will force one group of cells to more intensive work, but at the same time it will weaken the efficiency of the other, and in consequence blood glucose level will not change or may even increase significantly."

The discovery of the role of cannabinoids in the communication between alpha and beta cells gives hope for more effective treatment of diabetes by islet transplantation. Such allografts have already been performed: a portion of respective tissue is being recovered from a dead donor and placed under the mucosa of the recipient's stomach. Yet, the effects are not fully rewarding as beta cells of the implant often lose their identity: they are still alive, but can no longer produce insulin. After implantation of a foreign tissue a patient must take immunosuppressive drugs and the damage caused by such therapy often outweighs its gains. Scientists from the Nencki Institute hope that understanding the cannabinoid pathway will enable to significantly extend beta cells working time. If further studies validate these assumptions, the islet transplants could become a full-fledged method of diabetes treatment. Moreover, nowadays beta cells can be grown from stem cells derived from a patient's adipose tissue. Therefore, in future patients would not need to take drugs to prevent rejection of transplanted pancreatic islets.

This research was supported by National Science Centre, Poland, grant no UMO-2013/10/E/NZ3/00670.