Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin

Abstract

Xenin, a recently discovered peptide produced by specific endocrine cells of the duodenal mucosa, has shown exocrine, endocrine and motility effects in the gastroenteropancreatic system in animal experiments. The aim of the present investigation was to study the role of xenin in the regulation of duodenojejunal motility of humans. Twenty-nine healthy volunteers from the hospital staff gave informed consent to participate in this investigation. In 20 volunteers, we determined plasma concentrations of immunoreactive xenin at 15 min intervals over a mean time period of 8 h fasting and recorded the interdigestive motor activity of the duodenojejunum. In a double-blind randomized crossover study on other nine subjects, synthetic xenin in a dose of 4 pmol kg-1 min-1 or placebo was infused for 10 min intravenously in the interdigestive period and postprandially after a liquid meal. Duodenojejunal motility was recorded simultaneously. Predefined interdigestive xenin plasma peaks were found to be significantly associated with the phases III of the migrating motor complex. In the interdigestive period, xenin induced a premature phase III activity in each volunteer; this was followed by a second phase III in five out of nine subjects. In the postprandial state, xenin significantly increased contraction frequency and the percentage of aborally propagated contractions. These findings suggest a role of the peptide hormone xenin in modulating interdigestive and postprandial duodenojejunal motility in humans.

Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism

“…Xenin-25 also inhibits food intake in chicks, rats, and mice (25)(26)(27). In the single published human study, intravenous infusion of xenin-25 increased intestinal motility (28). This study did not report the effect of xenin-25 infusion on plasma insulin levels.…”

Metabolism and potency of xenin and of its reduced hexapseudopeptide Ψ fragment in the dog

“…We expect a further increase in efficacy. Previous experiments have suggested that xenin may be useful as a therapeutic agent in humans to stimulate intestinal motility (Feurle et al, 2001). …”

“…Whereas in the dog, xenin plasma concentrations are low and difficult to measure, immunoreactive xenin is detectable in the human circulation (Feurle et al, 1992;Feurle et al, 2003). Spontaneous peaks of xenin-immunoreactivity in human plasma have been observed in association with phase III of the interdigestive myoelectrical complex (Feurle et al, 2001) and elevated plasma concentrations have been demonstrated by radioimmunoassay high pressure liquid chromatography (HPLC) after feeding and sham feeding. (Feurle et al, 2003) In the present investigation, we examined the metabolism of xenin in the circulation of the anaesthetized dog.…”

The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus

“…Following a 10-min priming dose, each peptide(s) was continuously administered at a dose of 4 pmol/kg/min. The rationale for peptide dosing was based on published studies [11,12,34,35] as previously discussed [13]. Screening, group characteristics, experimental details, and glucose, insulin, C-peptide, glucagon, GIP, Xen, and insulin secretion rate (ISR) determinations were previously reported [13] and PP levels reported in the present study were measured in plasma samples collected in this earlier study.…”