Clinical trial NCT05900193: Sucralose and Lactisole Additions to OGTT in Humans
Official title: Activation and Inhibition of the Sweet Taste Receptor T1R2-T1R3 Differentially Affect Glucose Tolerance in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neat OGTT
OGTT With Added Sucralose
OGTT With Added Lactisole
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2023-06-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants were given oral glucose tolerance tests alone or with lactisole or sucralose in admixture with the glucose. All controls were within subjects in counterbalanced crossover design.
Primary purpose: BASIC_SCIENCE

Brief summary: In the present study, our objective was to determine whether T1R2-T1R3 influences glucose metabolism bidirectionally via hyperactivation with sucralose and inhibition with sodium lactisole in mixture with glucose loads during tolerance tests in humans. In 12 healthy participants we conducted oral glucose tolerance tests (OGTTs) of 75 g glucose with and without the addition of the T1R2-T1R3 agonist, sucralose (5 mM). We also conducted OGTTs in 10 healthy participants with and without the addition of a T1R2-T1R3 antagonist, sodium lactisole (2 mM). Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose, their sensitivities to sweetness inhibition by lactisole, and their BMIs.

Detailed description: The sweet taste receptor, T1R2-T1R3, is expressed in taste bud cells, where it conveys sweetness, and also in intestinal enteroendocrine cells, where it may facilitate glucose absorption and assimilation. There is evidence in mice through genetic knockout studies that T1r2-T1r3 is involved in endocrine and enteroendocrine responses to glucose loads. Yet, our understanding of the impact of T1R2-T1R3 on human glucose metabolism is less clear. In the present study, our objective was to determine whether T1R2-T1R3 influences glucose metabolism bidirectionally via hyperactivation with sucralose and inhibition with sodium lactisole in mixture with glucose loads during tolerance tests in humans. In 12 healthy participants we conducted oral glucose tolerance tests (OGTTs) of 75 g glucose with and without the addition of the T1R2-T1R3 agonist, sucralose (5 mM). We also conducted OGTTs in 10 healthy participants with and without the addition of a T1R2-T1R3 antagonist, sodium lactisole (2 mM). Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose, their sensitivities to sweetness inhibition by lactisole, and their BMIs. The addition of sucralose to glucose elevated plasma insulin responses to the OGTT. Sucralose-sensitive participants, those who rated sucralose as sweetest, had a more pronounced elevation in peak plasma insulin to sucralose + glucose with early increases in plasma glucose and insulin area-under-the-curve (AUC) within the first 15 minutes. In lactisole-sensitive participants, whose sweetness was suppressed by low levels of lactisole, the addition of lactisole to glucose in the OGTT decreased plasma glucose AUC. Participants with higher BMI (\>24 kg/m2) tended to be hyper-responsive to added sucralose, nearly doubling their peak levels of insulin to the sucralose + glucose OGTT . Manipulation of the T1R2-T1R3 receptor with a non-caloric agonist and an antagonist demonstrates that T1R2-T1R3 helps regulate glucose handling and metabolism in humans. Importantly, participants with BMI \> 24 kg/m2 tended to rate sucralose as sweeter and showed exaggerated insulin increases when it was added to their OGTT.

Eligibility criteria: Inclusion Criteria:

* Non-diabetic
* No metabolic disease
* Should not have exercised in past 24 hours.
* Should have undergone overnight fast.
* BMI \<30 kg/m2

Exclusion Criteria:

* Participants who reported consuming more than one serving of artificially sweetened beverages or snacks per day were excluded.
* Participants with diseases (e.g. metabolic syndrome and diabetes) and medications that may affect taste, digestion and absorption (e.g. anti-hypertensives, antibiotics, insulin, metformin, SGLT2 Inhibitors, sulfonylureas) were also excluded.
* Participants with BMI\>30 kg/m2 were excluded.

Primary outcomes:
measure: Plasma Glucose
timeFrame: 90 minutes
measure: Plasma Insulin
timeFrame: 90 minutes
measure: Plasma glucagon
timeFrame: 90 minutes
Secondary outcomes:
measure: Taste responsivity to sucralose
timeFrame: 30 minutes
measure: Taste inhibition by lactisole
timeFrame: 30 minutes
measure: Body-mass Index
timeFrame: 15 minutes
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers, Department of Nutritional Sciences
state: New Jersey
Study officials:
affiliation: Rutgers, The State University of NJ
name: Paul Breslin, PhD
role: PRINCIPAL_INVESTIGATOR
References: