Regulatory molecule enables control of insulin release via blue lights
People with diabetes rely on a precise adjustment of their blood sugar levels in order to avoid consequential damage to the disease as far as possible. To regulate the insulin balance, scientists at the Ludwig Maximillians University (LMU) in Munich have now developed a type of optical switch that causes an increased insulin release when blue light is supplied.
According to a message from the LMU, the researchers have equipped a receptor that is important for the insulin household with the optical switch, which is activated by blue lights and increases the insulin release. The scientists led by Dirk Trauner, Professor of Chemical Biology and Genetics at the LMU, in cooperation with researchers led by David Hodson from the Imperial College London, “made a molecule controllable with light, with the help of which GLP-1R can be optically regulated and the insulin release increased “, So the announcement of the LMU. Their results were published in the journal "Angewandte Chemie".
Regulation of insulin release
The widespread disease type 2 diabetes affects millions of people worldwide and the treatment options have so far been limited to controlling the blood sugar level. Healing is not possible. As a result of the chronic metabolic disorder, there is an increased blood sugar level "because the body cells no longer adequately release or react to insulin," explain the LMU researchers. The receptor GLP-1R plays a decisive role in regulating insulin release in the body and this could also be important for the treatment of type 2 diabetes. In their experiments, the scientists therefore equipped the receptor with a molecule that functions as an optical switch. "We use a so-called allosteric center of the GLP-1R as the docking point for our new molecular switch," explains Johannes Broichhagen, first author of the study.
Molecular switch developed
According to the researchers, the allosteric center is to be understood as a specific region of the GLP-1R to which regulatory molecules bind and which can thereby cause a structural change in the receptor. The allosteric regulation can significantly increase the drug specificity of receptors such as GLP-R1. "So far, however, drug development has been hampered by the fact that allosteric binding sites cannot be controlled precisely enough," explains Prof. Dirk Trauner. Here, however, a decisive step forward has been made by equipping a synthetic binding partner of the allosteric center with a molecular switch that reacts to light.
Control of insulin release through the supply of light
According to the researchers, the new “PhotoETP” molecule enables precise optical control of the GLP-1R receptor. The new photo switch binds in its inactive form to the allosteric center of GLP-1R and is activated when illuminated with blue light. This leads to a change in the structure of the receptor, which activates it and initiates an increased release of insulin. Broichhagen reports that the process is easy to control because light can be controlled very precisely. In the next step, the researchers are now planning to develop a variant of their switch that responds to red light, which, in contrast to blue light, also reaches deeper tissue layers. Furthermore, the synthesis of additional, structurally similar molecules is planned. "GLP-1R belongs to the large class of G protein-coupled receptors, many of which are pharmaceutical target receptors," emphasizes Prof. Trauner. The molecule “PhotoETP” is therefore a promising template for the development of other potentially therapeutically usable photoswitchable molecules for receptors of this class. (fp)