Effects of Combined Intragastric Administration of Quinine with L-Leucine or L-Isoleucine on the Glycemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Healthy Males.

BACKGROUND

The amino acids, L-leucine (Leu) and L-isoleucine (Ile), and the bitter substance, quinine, reduce postprandial glucose, stimulate insulin, and/or slow gastric emptying. Whether combining these stimuli can enhance these effects is not known.

OBJECTIVES

We investigated whether combined intragastric administration of quinine with Leu or Ile, each in submaximal dose, would reduce the plasma glucose response to a mixed-nutrient drink more than each compound individually, associated with greater insulin stimulation and/or slowing of gastric emptying.

METHODS

Fifteen healthy, lean males were recruited for each of the 2 study parts. They received on 4 separate occasions, 1) 300 mg quinine hydrochloride ("QHCl"), 2) 5g ("Leu"; part A) or 5g ("Ile"; part B), 3) combination of 1) + 2) ("QHCl + Leu" or "QHCl + Ile"), or 4) control intragastrically, in a randomized, double-blind fashion. At t = -60 min, either QHCl or control was administered, and 30 min later (at t = -30 min), amino acid or control was administered. At t = -1 min, participants consumed a mixed-nutrient drink labeled with sodium acetate-1-13C for measurement of gastric emptying by breath test. Plasma glucose and insulin were measured at baseline (i.e. t = -60 min), for 60 min before the drink, and for 180 min postdrink. Breath samples were collected at baseline and postdrink, for subsequent analysis of 13CO2.

RESULTS

QHCl, QHCl + Leu, and QHCl + Ile delayed the early rise in plasma glucose compared with control, Leu, and Ile (all P < 0.05). QHCl + Leu and QHCl + Ile stimulated insulin compared with QHCl, Leu, and control (all P < 0.05), but did not affect gastric emptying. The early glucose response [area under the curve (AUC), t = 0‒30 min (AUC0‒30 min)] was related directly to early gastric emptying (AUC0‒30 min) (R > 0.41, P < 0.01).

CONCLUSIONS

In healthy males, although combining QHCl with Leu or Ile, in the doses used, did not enhance their glucose-lowering effects, even small changes in the early gastric emptying rate and insulin stimulation appear to contribute to postprandial glucose-lowering. This trial was registered at clinicaltrials.gov as NCT05720390 and NCT05682339.