Effect of motilin on gastric emptying in patients with diabetic gastroparesis

Abstract

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol · kg−1 · min−1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 ± 6 to 22 ± 11 minutes (P < 0.01) and for solids from 111 ± 4 to 51 ± 12 minutes (P < 0.01). The mean increase in plasma motilin levels was 1315 ± 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol · kg−1 · min−1. In the control experiments, basal motilin levels (173 ± 17 pg/ mL) were within the normal range but increased steadily postprandially, reaching 321 ± 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 ± 217 vs. 279 ± 66 pg/mL (P < 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.