Supraphysiological effects of pancreatic polypeptide on gastric motor function and nutrient tolerance in humans

Abstract

Pancreatic polypeptide (PP) is known to affect food intake. In this exploratory study, we set out to investigate its supraphysiological effect on food tolerance, gastric accommodation, and emptying. In 12 healthy volunteers, 0, 3, or 10 pmol*kg^-1 *min^-1 PP was administered intravenously (PP0, PP3 or PP10). Thirty minutes thereafter, nutrient drink infusion (60 ml*min^-1 ) through a nasogastric feeding tube was started until maximum satiation. Gastric accommodation was assessed by measuring the intragastric pressure (IGP; nasogastric manometry). In a separate test, the effect of PP0 or PP10 on gastric emptying was tested in 10 healthy volunteers and assessed using the ¹³ C breath test. Results are presented as mean ± SEM, and p < 0.05 was considered significant. For the IGP test, PP increased ingested nutrient volume: 886 ± 93, 1059 ± 124, and 1025 ± 125 ml for PP0, PP3, and PP10, respectively (p = 0.048). In all groups, Nadir IGP values were reached upon food intake (transformed values: 1.5 ± 0.2, 1.7 ± 0.3, and 1.6 ± 0.3 mmHg for PP0, PP3, and PP10, respectively; NS) to return to baseline thereafter. For the gastric emptying study, volunteers ingested a similar nutrient volume: 802 ± 119 and 1089 ± 128 ml (p = 0.016), and gastric half-emptying time was 281 ± 52 and 249 ± 37 min for PP0 and PP10, respectively (NS). No significant correlation between tolerated nutrient volume and IGP drop (R² < 0.01; p = 0.88 for PP0 vs. PP3 and R² =0.07; p = 0.40 for PP0 vs. PP10, respectively) or gastric half-emptying time (R² = 0.12; p = 0.32) was found. A supraphysiological PP dose enhances food tolerance; however, this effect is not mediated through gastric motility. CLINICAL TRIAL REGISTRY NUMBER: NCT03854708 is obtained from clinicaltrials.gov.

Keywords: food tolerance; gastric accommodation; gastric emptying; pancreatic polypeptide.

FIGURE 1

The change of IGP during the first 30 min of treatment in the fasted state. The values are changes from the fasted baseline IGP (average value of 5 min before the treatment). Data are presented as mean ± SEM (n = 12). IGP, intragastric pressure; PP, pancreatic polypeptide; ND, nutrient drink

FIGURE 2

The change of IGP from the start of nutrient drink infusion until 25 min. The values are changes from a baseline pressure (average value of 5 min before nutrient drink infusion). Data are presented as mean ± SEM (n = 12). IGP, intragastric pressure; PP, pancreatic polypeptide; ND, nutrient drink

FIGURE 3

Human PP plasma concentrations before treatment of placebo (PP0) and 3 pmol*kg⁻¹*min⁻¹ PP (PP3) and 10 pmol*kg⁻¹*min⁻¹ PP (PP10) 5 min before and immediately after intragastric ND infusion and 6 h after the ND infusion. Data are represented as mean ± SEM (n = 6) and p < 0.05 was considered significant. PP, pancreatic polypeptide

FIGURE 4

Appetite‐related sensations scored during the gastric emptying experiment on visual analogue scale scores (0–100 mm) between placebo (PP0) and 10 pmol*kg⁻¹*min⁻¹ PP (PP10). T₀ represents the start of the intragastric nutrient drink infusion. Data are represented as mean ± SEM (n = 9), and an effect is considered significant if p < 0.05. (a) Hunger sensations; (b) Prospective food intake sensations and (c) Satiety sensations. PP, pancreatic polypeptide