Sucralose and Lactisole Additions to OGTT in Humans
Condition: Neat OGTT; OGTT With Added Sucralose; OGTT With Added Lactisole
Study type: Interventional

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.
    

Intervention name(s): TAS1R2/3 agonist or antagoinst admixture to oral glucose tolerance test
Intervention type(s): Dietary Supplement
Intervention description(s): 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.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
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.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science