Summary: The sweet taste receptor, TAS1R2-TAS1R3, plays a dual role in regulating glucose metabolism. Stimulating this receptor with sucralose accelerates insulin release, while inhibiting it with lactisole slows it.
This finding suggests that targeting TAS1R2-TAS1R3 could offer new therapeutic avenues to manage metabolic disorders such as diabetes.
Highlights:
- The sweet taste receptor TAS1R2-TAS1R3 influences glucose metabolism in humans.
- Stimulation of the receptor speeds up insulin release, while inhibition slows it.
- This discovery could lead to new treatments for metabolic disorders like diabetes.
Source: Monell Chemical Senses Center
The Monell Chemical Senses Center’s rich research portfolio on sweet taste goes back a long way: Monell scientists were one of four teams in 2001 that discovered and described the mammalian sweet taste receptor, TAS1R2-TAS1R3.
Twenty years later, in 2021, two papers published in Mammalian Genome by Monell researchers covered the genetics of sugar-loving mice.
The sweet taste receptor, expressed in taste bud cells, transmits sweetness in the mouth when activated.
Earlier this month, a study conducted PLOS Oneled by another Monell researcher, studied how the sweet taste receptor could be the first stop in a sugar metabolic monitoring system.
The receptor is also expressed in some intestinal cells, where it can facilitate the absorption and assimilation of glucose, as part of this system.
The team found that stimulation and inhibition of TAS1R2-TAS1R3 demonstrate that it helps regulate glucose metabolism in humans and could have implications in the management of metabolic disorders such as diabetes. Glucose is the main type of sugar found in human blood, making it a key energy source for cells.
“Our goal was to determine whether TAS1R2-TAS1R3 influences glucose metabolism in two directions,” said Monell Fellow Paul Breslin, Ph.D., professor of nutritional sciences at Rutgers University and senior author of the paper. .
They showed that a TAS1R2-TAS1R3 agonist (sucralose, a calorie-free sweetener) or a TAS1R2-TAS1R3 antagonist (lactisole, a sodium salt that inhibits sweet taste) mixed with a glucose meal acutely altered the glucose tolerance in humans in different ways.
Here, an agonist binds to a receptor and stimulates a cell and an antagonist binds to a receptor and prevents stimulation.
“The novelty of our findings is that the receptor we studied in this experiment affects blood sugar and insulin differently during a glucose-containing meal, depending on whether it is stimulated or inhibited,” Breslin said.
This work provides further evidence that taste receptors help regulate metabolism and nutrient handling.
Plasma insulin levels were measured in study participants undergoing an oral glucose tolerance test (OGTT), which tracks blood sugar levels before and after a person drinks a liquid meal containing glucose.
Participants’ ratings of the perceived sweetness of sucralose correlated with early increases in blood glucose, as well as increases in plasma insulin levels when sucralose was added to OGTT. The added sucralose tended to accelerate the release of insulin into the glucose load.
On the other hand, participants’ sensitivity to lactisole-induced sweet taste inhibition correlated with a decrease in plasma glucose levels. Lactisole also tended to slow down insulin release.
“When glucose stimulates taste receptors before being absorbed by the body, signals are sent via the mouth and intestine to regulatory organs such as the pancreas. Perhaps we could design ways to use TAS1R2-TAS1R3 to help the body better manage glucose by anticipating when glucose will appear in the blood,” Breslin said.
When the body senses glucose, it speeds up its absorption to deliver it to tissues that might need it and possibly to prevent glucose from moving too far along the gut, which might not be good for maintaining a microbiome healthy intestinal.
“This system is elegant in its simplicity,” Breslin said. The same taste receptor is present throughout the body: the mouth, gastrointestinal tract, pancreas, liver, and fat cells, the latter three being major metabolic regulatory tissues, all of which are part of metabolic monitoring of the body 24/7.
Is there a relationship between a person’s state of health and the activity of their TAS1R2-TAS1R3 receptors? The study authors say this is likely, suggesting that the degree of receptor activation acutely influences plasma glucose and insulin levels and their timing of onset, which is important for metabolic health.
The team maintains that, in general, current dietary habits of excessive consumption of foods and drinks high in sucrose, high fructose corn syrup, and strong sweeteners could hyperstimulate TAS1R2-TAS1R3, contributing to poor regulation of blood glucose.
This could lead to a diagnosis of metabolic syndrome, a cluster of risk factors including high blood sugar and insulin insensitivity (along with obesity, hypertension, and increased plasma fats) that increase the risk of disease. heart disease, stroke and diabetes.
The authors say future studies should examine the effects of TAS1R2-TAS1R3 stimulation and inhibition in individuals at risk for metabolic syndrome to determine the therapeutic potential of manipulating TAS1R2-TAS1R3 for better metabolic control. rather than worse.
“Studies like these, using Monell’s technical capabilities and deep expertise in chemical senses, show that the sweet taste receptor TAS1R2-TAS1R3 helps regulate glucose differently, depending on the sweetness of the food or drinking,” Breslin said.
The team’s hope is to apply what they’ve learned to make what we eat and drink healthier.
“A small positive metabolic change can add much more to human life and health when compounded over decades and millions of people,” Breslin said.
With Breslin, co-authors are Emily C. Hanselman and Matthew C. Kochem, Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ.
About this research news in neuroscience and metabolism
Author: Karen Krieger
Source: Monell Chemical Senses Center
Contact: Karen Kreeger – Monell Chemical Senses Center
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affect glucose tolerance in humans” by Matthew C. Kochem et al. PLOS One
Abstract
Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affects glucose tolerance in humans
The sweet taste receptor, TAS1R2-TAS1R3, is expressed in taste bud cells, where it transmits sweetness, as well as in intestinal enteroendocrine cells, where it can facilitate the absorption and assimilation of glucose.
In the present study, we aimed to determine whether TAS1R2-TAS1R3 influences glucose metabolism bidirectionally via hyperactivation with 5 mM sucralose (n = 12) and inhibition with 2 mM lactisole sodium (n = 10). mixed with 75 g of glucose during oral intake. glucose tolerance tests (OGTT) in healthy humans.
Plasma glucose, insulin, and glucagon were measured before, during, and after OGTT up to 120 minutes after the meal.
We also assessed individual participants’ sweet taste responses to sucralose and their sensitivity to lactisole’s sweet taste inhibition. Addition of sucralose to glucose increased plasma insulin responses to OGTT (F(1,11) = 4.55, p = 0.056).
Sucralose sweetness indices were correlated with early increases in blood glucose (R2 = 0.41, p<0.05), as well as an increase in plasma insulin (R2 = 0.38, p < 0.05) when sucralose was added to OGTT (AUC 15 minutes).
Sensitivity to lactisole sweet taste inhibition was correlated with a decrease in blood glucose (R2 = 0.84, p<0.01) when lactisole was added to OGTT for the entire test duration (AUC 120 minutes).
In summary, stimulation and inhibition of the TAS1R2-TAS1R3 receptor demonstrate that TAS1R2-TAS1R3 helps regulate glucose metabolism in humans and may have translational implications for metabolic disease risk.