Researchers led by Javier Ramón-Azcón from the Institute for Bioengineering of Catalonia develop a “gym on a chip” that will help to study diabetes and find new drugs to treat the disease. The dispositive allow to study, in vivo, the crosstalk among different organs. In this paper, researchers combine muscle and pancreatic cells on a single chip and demonstrates that insulin production by the pancreas during exercise is induced by the contraction of muscle cells.
According to the World Health Organisation, 422 million people worldwide suffer from diabetes mellitus, and 1.5 million deaths each year are directly associated with the disease. Diabetes is a complex metabolic disease characterised by a high accumulation of glucose in the blood resulting from a failure in the production or activity of insulin. Insulin, in turn, is a hormone produced, stored and released by the pancreas, which enables glucose to enter the different cells of the body to provide them with the energy they need to function properly. Muscle is one of the main targets of insulin and is crucial in the overall maintenance of glucose levels throughout the body.
The development of new drugs to prevent and treat diabetes must be based on tools that take into account the communication between the pancreas and other organs in order to recreate the details of the disease. In a recent study published in the Advanced Materials Technology journal, IBEC researchers led by Juan M. Fernández-Costa and Javier Ramon-Azcon from the “Biosensors for Bioengineering” group, have developed a “multi-organ-on-chip” that allows, in a single device, to study the communication between the insulin-producing cells of the pancreas and the muscle cells. By using this innovative “gym on a chip”, researchers found that muscle cells contraction caused by electric stimulation directly induces the production of insulin by pancreatic cells.
The “gym on a chip”
The “multi-organ-on-chip” device engineered by the researchers have one compartment with skeletal muscle cells and another one with pancreatic islets composed of beta cells, which produce insulin. As these cells grow and develop, they form 3D structures that simulate a “mini-organ” inside the chip.
The muscle cells of the “multi-organ-on-chip” are connected to an electrical stimulator that simulates physical exercise and induces their contraction. In addition, the device is also integrated with a complex biosensor platform capable of monitoring insulin levels produced by pancreatic cells, and interleukin-6 (IL-6) levels without the need of external labelling. IL-6 is a regulatory protein that is produced by the muscle and signals the pancreas to increase insulin production. In other words, during exercise, IL-6 moves from the muscle to the pancreas to stimulate insulin production.
“With our “gym on a chip” we demonstrate that insulin secretion by pancreatic islets during exercise is dynamically mediated by the contractile activity of muscle cells and not by other intermediates”. Juan M. Fernández-Costa, first author of the study.
The new chip is a powerful tool for diabetes drug development and testing, and it allows personalised modelling of the disease by using patient’s own cells. With this model, researchers and clinicians will have the possibility to study diabetes following a new approach, by combining different cell types, and study in detail why insulin production by the pancreas sometimes fails.
In the future, the “muti-organ-on-chip” could also be used to study communication between other organs in the context of various metabolic diseases, providing a promising platform for new drug screening and personalised medicine.
Reference article: Training-on-a-Chip: A Multi-Organ Device to Study the Effect of Muscle Exercise on Insulin Secretion in Vitro. Juan M. Fernández-Costa, María A. Ortega, Júlia Rodríguez-Comas, Gerardo Lopez-Muñoz, Jose Yeste, Lluís Mangas-Florencio, Miriam Fernández-González, Eduard Martin-Lasierra, Ainoa Tejedera-Villafranca, and Javier Ramon-Azcon. Adv. Mater. Technol. 2022, 2200873.