Sucralose and Lactisole Additions to OGTT in Humans (SLOGTT)

Activation and Inhibition of the Sweet Taste Receptor T1R2-T1R3 Differentially Affect Glucose Tolerance in Humans

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.

Study Overview

• Status: Completed
• Conditions: Neat OGTT; OGTT With Added Sucralose; OGTT With Added Lactisole
• Intervention / Treatment: Dietary supplement: TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers, Department of Nutritional Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving oral glucose tolerane tests with TAS1R agonists; Participants received a standard oral glucose tolerance test alone and with the addition of the TAS1R2/3 agonist sucralose in admixture	Dietary supplement: TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test; Participants drank a glucose beverage for an oral glucose tolerance test along or with admixture with the TAS1R2/3 agonist sucralose or the TAS1R2/3 antagonist lactisole.
Experimental: Participants receiving oral glucose tolerane tests with TAS1R antagonists; Participants received a standard oral glucose tolerance test alone and with the addition of the the TAS1R2/3 antagonist lactisole in admixture	Dietary supplement: TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test; Participants drank a glucose beverage for an oral glucose tolerance test along or with admixture with the TAS1R2/3 agonist sucralose or the TAS1R2/3 antagonist lactisole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose	Repeated plasma blood draws during OGTT will determine plasma glucose	90 minutes
Plasma Insulin	Repeated plasma blood draws during OGTT will determine plasma insulin	90 minutes
Plasma glucagon	Repeated plasma blood draws during OGTT will determine plasma glucagon	90 minutes

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Paul Breslin, PhD, Rutgers, the State University of NJ

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2016
• Primary Completion (Actual): September 18, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: June 2, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 16-105mc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Journals require de-identified data be made available to others.
• IPD Sharing Time Frame: Available upon request
• IPD Sharing Access Criteria: Contact the PI at breslin@monell.org
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No