Commonly used in agriculture and medicine, these chemical compounds were not previously known to act on the T1R3 receptor.
The T1R3 receptor is a critical component of both the sweet taste receptor and the umami (amino acid) taste receptor. First identified on the tongue, emerging evidence indicates that T1R3 and related taste receptors also are located on hormone-producing cells in the intestine and pancreas.
These internal taste receptors detect nutrients in the gut and trigger the release of hormones involved in the regulation of glucose homeostasis and energy metabolism.
“Compounds that either activate or block T1R3 receptors could have significant metabolic effects, potentially influencing diseases such as obesity, type II diabetes and metabolic syndrome,” noted Monell geneticist and study leader Bedrich Mosinger, M.D., Ph.D.
In the study, published online in the Journal of Medicinal Chemistry, researchers tested the ability of two classes of chemical compounds to block the T1R3 receptor. The compounds – fibrates and phenoxy-herbicides – were selected based on their strong structural similarity to lactisole, a sweet taste inhibitor that exerts its taste effects by blocking T1R3.
Fibrates are a class of drugs frequently used to treat lipid disorders such as high blood cholesterol and triglycerides. Phenoxy-herbicides are used in agriculture to control broad-leaf weeds; the best known, 2,4-D, is one of the most extensively used herbicides worldwide.
Using an in vitro preparation, the researchers found that both classes of compounds potently blocked activation of the human sweet taste receptor, acting at micromolar concentrations to inhibit binding of sugars to the T1R3 component of the receptor.
Additional testing revealed that the inhibitory effect of both fibrates and phenoxy-herbicides on the T1R3 receptor is specific to humans. That is, the ability of these compounds to block the receptor did not generalize across species to the rodent form of the receptor.
Mosinger commented on the implications of the findings and noted the importance of testing chemicals intended for human use on human tissues. “The metabolic consequences of short- and long-term exposures of humans to phenoxy-herbicides are unknown. This is because most safety tests were done using animals, which have T1R3 receptors that are insensitive to these compounds,” he said.
The ability of fibrate drugs to interact with T1R3 receptors also was previously unknown. The study findings suggest that these receptors might be an important pharmacological target of first-generation fibrates, such as clofibrate, which were believed to act on a different receptor to affect lipid metabolism. Newer fibrate drugs are more specific for the second receptor and interact less with the T1R3 receptor.
Mosinger points out that little is known about how T1R3 blockade affects hormone levels and metabolism. “Given the number of compounds used in agriculture, medicine and the food industry that may affect human T1R3 and related receptors, more work is needed to identify the health-related effects of exposure to these compounds,” he said.
Also contributing to the study were first author Emeline Maillet from the Department of Neuroscience at Mount Sinai School of Medicine and co-author Robert Margolskee of Monell.
Funding was provided by the National Institute on Deafness and Other Communication Disorders and the National Institute of Diabetes and Digestive and Kidney Diseases.
The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. Monell advances scientific understanding of the mechanisms and functions of taste and smell to benefit human health and well-being. Using an interdisciplinary approach, scientists collaborate in the programmatic areas of sensation and perception; neuroscience and molecular biology; environmental and occupational health; nutrition and appetite; health and well-being; development, aging and regeneration; and chemical ecology and communication.
Leslie Stein | Newswise Science News
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Trade Fair News
16.01.2017 | Automotive Engineering
16.01.2017 | Life Sciences