Background:
Glucose is a natural
ligand for sweet taste receptors (STRs) that are expressed on the tongue and in the gastrointestinal tract. Whether STRs directly contribute to the regulation of
glucose homeostasis in response to
glucose ingestion is unclear.Objective: We sought to determine the metabolic effects of the pharmacologic inhibition of STRs in response to an oral
glucose load in healthy lean participants.Design: Ten healthy lean participants with a body mass index (in kg/m2) of 22.4 ± 0.8 were subjected to an oral-
glucose-tolerance test (OGTT) on 4 separate days with the use of a randomized crossover design. Ten minutes before the 75-g OGTT, participants consumed a preload
solution of either 300 parts per million (ppm)
saccharin or water with or without the addition of 500 ppm
lactisole, a human-specific inhibitor of STRs. When present,
lactisole was included in both the preload and OGTT solutions. We assessed plasma responses of
glucose,
insulin,
C-peptide,
glucagon,
glucagon-like peptides 1 and 2, gastric inhibitory
peptide,
acetaminophen, and
3-O-methylglucose. With the use of mathematical modeling, we estimated gastric emptying,
glucose absorption, β-cell function,
insulin sensitivity and clearance, and the portal
insulin:
glucagon ratio.Results: The addition of
lactisole to the OGTT caused increases in the plasma responses of
insulin (P = 0.012),
C-peptide (P = 0.004), and the
insulin secretory rate (P = 0.020) compared with the control OGTT. The addition of
lactisole also caused a slight reduction in the
insulin sensitivity index independent of prior
saccharin consumption (P < 0.025). The ingestion of
saccharin before the OGTT did not alter any of the measured variables but eliminated the effects of
lactisole on the OGTT.Conclusion: The pharmacologic inhibition of STRs in the gastrointestinal tract alters
insulin responses during an oral
glucose challenge in lean healthy participants. This trial was registered at clinicaltrials.gov as NCT02835859.