Elevated Circulating Levels of Motilin are Associated with Diabetes in Individuals after Acute Pancreatitis

Aim The study aimed to investigate the associations between glycaemic control after acute pancreatitis and gastrointestinal motility, using plasma motilin concentration and gastroparesis cardinal symptom index score as proxies. Methods This cross-sectional study recruited a total of 93 individuals after acute pancreatitis. Gastroparesis cardinal index scores, demographic and anthropometric factors, as well as pancreatitis-related factors were analysed. Fasting venous blood was collected to measure motilin, glycated haemoglobin, and fasting blood glucose. Linear regression analyses were conducted to investigate the associations between glycaemic control and gastrointestinal motility in unadjusted and adjusted models. Results Motilin was significantly higher in individuals with diabetes across all adjusted models, with the highest ß-coefficient (95% confidence interval) of 588.89 (138.50, 1039.28); P=0.010. Fasting blood glucose was significantly associated with motilin across all models, with the highest ß-coefficient (95% confidence interval) of 156.30 (55.49, 257.10); P=0.002. Glycated haemoglobin was significantly associated with motilin in one adjusted model with ß-coefficient (95% confidence interval) of 18.78 (1.53, 36.02); P=0.033. Gastroparesis cardinal symptom index was not significantly associated with any measure of glycaemic control. Conclusions Diabetes in individuals after acute pancreatitis appears to be characterised by elevated plasma motilin but not gastroparesis cardinal symptom index. The role of motilin in this setting warrants further investigations.

Interaction between Pirenzepine and Ninjinto, a Traditional Japanese Herbal Medicine, on the Plasma Gut-Regulated Peptide Levels in Humans

The Japanese herbal medicine (Kampo) Ninjinto has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. The pharmacological effects of Ninjinto on the gastrointestine are due to changes in the levels of gut-regulated peptide, such as motilin, somatostatin, calcitonin gene-related peptide (CGRP), substance P, and vasoactive intestinal polypeptide (VIP). The release of these peptides is controlled by acetylcholine (ACh) from the preganglionic fibers of the parasympathetic nerve. Thus, we examined the effects of the selective M1 muscarinic receptor antagonist pirenzepine on the elevation of Ninjinto-induced plasma the area under the plasma gut-regulated peptide concentration-time curve from 0 to 240 min () in humans. Oral pretreatment with pirenzepine significantly reduced the Ninjinto-induced elevation of plasma motilin and substance P release (). Combined treatment with Ninjinto and pirenzepine significantly increased the release of plasma somatostatin () compared with administration of Ninjinto alone or placebo. Ninjinto appeared to induce the release of substance P and motilin into plasma mainly through the activation of M1 muscarinic receptors, and pirenzepine may affect the pharmacologic action of Ninjinto by the elevation of plasma substance P, motilin, and somatostatin.

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [d-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [d-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.