Sucralose and Lactisole Additions to OGTT in Humans

Not Applicable

Completed

• Conditions: Neat OGTT; OGTT With Added Sucralose; OGTT With Added Lactisole
• Interventions: Dietary Supplement: TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test

• Registration Number: NCT05900193
• Lead Sponsor: Rutgers, The State University of New Jersey

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.

Study Timeline

• Study Start: 2016-07-17
• Primary Completion: 2017-09-18
• Study Completion: 2017-10
• Status Verified: 2023-06
• Study First Submitted: 2023-06-02
• Study First Submitted QC: 2023-06-02
• Last Update Submitted: 2023-06-02
• Study First Posted: 2023-06-12
• Last Update Posted: 2023-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Participants receiving oral glucose tolerane tests with TAS1R agonists	TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test	Participants received a standard oral glucose tolerance test alone and with the addition of the TAS1R2/3 agonist sucralose in admixture
Participants receiving oral glucose tolerane tests with TAS1R antagonists	TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test	Participants received a standard oral glucose tolerance test alone and with the addition of the the TAS1R2/3 antagonist lactisole in admixture

Primary Outcome Measures

Name	Time	Method
Plasma Insulin	90 minutes	Repeated plasma blood draws during OGTT will determine plasma insulin
Plasma Glucose	90 minutes	Repeated plasma blood draws during OGTT will determine plasma glucose
Plasma glucagon	90 minutes	Repeated plasma blood draws during OGTT will determine plasma glucagon

Secondary Outcome Measures

Name	Time	Method
Body-mass Index	15 minutes	Individual participant BMI was calculated
Taste responsivity to sucralose	30 minutes	How sweet sucralose tastes to participants is reported
Taste inhibition by lactisole	30 minutes	How effectively lactisole inhibits sweet taste for individual participants is assessed

Trial Locations

Locations (1)

Rutgers, Department of Nutritional Sciences; 🇺🇸 New Brunswick, New Jersey, United States