Cells chat via cannabinoids – also about your future diabetes
Pancreatic cells, regulating blood glucose levels, exchange information via endogenously synthesized cannabinoids, substances present, inter alia, in cannabis. Chemical signals pathway discovered by a group of researchers from the Nencki Institute in Warsaw have proved to increase the ability of cells to produce insulin, and in embryos – even to affect pancreatic islets formation. The discovery may be leading to the development of more effective methods of dealing with diabetes.
The level of glucose in human blood depends on the continuous cooperation between two types of cells in the pancreas. Alpha cells secrete glucagon hormone that increases glucose in blood, while the beta cells secrete insulin, the hormone decreasing glucose concentration. Scientists from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw have recently discovered that the alpha and beta cells communicate with each other, and the central role in this communication is played by cannabinoids – organic compounds that occur in nature also in inflorescences of cannabis. In recent studies, carried out in cooperation with institutes from Sweden, Austria, Italy and the United States, it has also been shown that cannabinoids have an impact on the identity of the beta cells, and in human embryos they may lead to significant changes in the architecture of a forming pancreatic islets.
“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 prestigious American “Proceedings of the National Academy of Sciences USA” (PNAS) journal, 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.
The Nencki Institute of Experimental Biology of the Polish Academy of Sciences has been established in 1918 and is the largest non-university centre for biological research in Poland. Priority fields for the Institute include neurobiology, neurophysiology, cellular biology and biochemistry and molecular biology – at the level of complexity from tissue organisms through cellular organelles to proteins and genes. There are 31 labs at the Institute, among them modern Laboratory of Confocal Microscopy, Laboratory of Cytometry, Laboratory of Electron Microscopy, Behavioural and Electrophysiological Tests. The Institute is equipped with state-of-the-art research equipment and modernized animal house, where lab animals are bred, also transgenic animals, in accordance with the highest standards. Quality of experiments, publications and close ties with the international science community, place the Institute among the leading biological research centres in Europe.
Prof. Agnieszka Dobrzyń
Nencki Institute of Experimental Biology
tel. +48 22 5892261
Nencki Institute’s Laboratory of Cell Signaling and Metabolic Disorders website.
The official website of the Nencki Institute of Experimental Biology in Warsaw.
Press service of the Nencki Institute of Experimental Biology in Warsaw.
“Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture”; K. Maleńczyk, E. Keimpema, F. Piscitelli, D. Calvigioni, P. Björklund, K. Mackie, V. Di Marzo, T. G. M. Hökfelt, A. Dobrzyń, T. Harkany; Proceedings of the National Academy of Sciences (PNAS), 112(45):E6185-94, 2015 Nov 10; DOI: 10.1073/pnas.1519040112
Cannabinoids, organic compounds occurring i.a. in cannabis, play a major role in many stages of type 2 diabetes development. In the picture: Prof. Agnieszka Dobrzyn from the Nencki Institute of Experimantal Biology in Warsaw in the lab. (Source: Nencki Institute, Grzegorz Krzyżewski)