Taste bud protein could unlock next-gen sweeteners and help control blood sugar, flag researchers

28 Jun 2021 --- US scientists at Van Andel Institute (VAI) are one step closer to developing new low-calorie alternative sweeteners that mimic sugar by activating sensory circuits in the brain and gut. The team has published the first-ever high-resolution images of TRPM5, a specialized protein concentrated in the taste buds, where it helps relay messages to and from cells.

The images also reveal two areas that may serve as targets for new medications that help control blood sugar in diabetes. 

“It will take multiple years to accomplish this project. We hope that more industries will take note of this urgent need and develop ‘real sugar’-like sweeteners to benefit human health and combat obesity and diabetes,” Wei Lü, associate professor at VAI and co-corresponding author of the study, tells NutritionInsight.The images reveal two areas that may serve as targets for new medications (Source: The Lü Lab and the Du Lab at VAI). 

Guiding important signals
TRPM5 is the cornerstone of taste signaling, which itself has a much larger role in the body than is often recognized, Lü continues.

When the tongue encounters a taste, specialized cells on the tongue called taste receptors send messages about that taste to the brain. TRPM5 is a key part of the complex process that ushers these important signals on their way to the brain’s sensory processing center.

Taste perception also occurs in certain pancreatic cells, which regulates insulin secretion, for example. This helps control blood sugar levels. 

Similar cells, called tuft cells, also coat the linings of the intestine, lungs and gallbladder, where they use TRPM5 and related proteins to sense the sugar-like byproducts of parasitic infections and trigger immune responses to deal with the threat.

Sweeteners in demand
Lü argues that existing artificial sweeteners have not completely succeeded in replacing sugar because they are not as satisfying as real sugar.

“The reason for this is that we taste real sugar not only through our tongue but also through our intestines. These two complementary but independent systems send taste signals to the brain that make us feel satisfied.”

However, artificial sweeteners can only act on the tongue to trick the brain, but not on the intestines. As a result, they do not result in the same satisfaction as sugar but may instead lead to boosting our appetite and eventually increasing caloric intake. 

“Therefore, there is an urgent need to develop new low-calorie substitutes that mimic the way real sugar acts on the brain,” Lü explains. To date, Lü and Du laboratories have solved the structures of three of the eight known TRPM proteins. 

Impacting insulin?
Many low-calorie sweeteners already exploit certain taste receptors. Lü points out that sucralose, aspartame and acesulfame-K bind to and activate sweet taste receptors. 

“Another example related to our newly published TRPM5 study is stevia and its derivatives, which are natural products extracted from the leaves of the plant Stevia rebaudiana. Stevia and its derivatives act on both sweet taste receptors and the TRPM5 channel.”

The preliminary research suggests that some artificial sweeteners trigger insulin secretion. Juan Du, associate professor at VAI and co-corresponding author of the study, says that this is because sweet taste receptors and the TRPM5 channel exist in the taste buds and in pancreatic beta cells. 

“Ingestion of these artificial sweeteners may increase the risk of insulin resistance. More studies are needed to provide a full picture about the pros and cons of sweeteners,” she concludes.

The long-term safety of sweeteners has long been a hot-button topic within the nutrition industry, with the microbiome emerging as a particular point of concern. 

However, technology has been accelerating innovation in this area. Last summer, Joywell Foods gained funding for its sweet fruit protein technology platform.

Meanwhile, DouxMatok improves the efficiency of sugar delivery to the sweet taste receptors. This enhances the perception of sweetness, enabling substantial sugar reduction without compromising taste, mouthfeel or texture.

By Katherine Durrell