Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients.

BACKGROUND: Increased intestinal permeability was described in several intestinal auto-immune conditions. There are very few and contradictory reports about type I diabetes mellitus, an auto-immune condition sometimes associated with celiac disease. AIMS: To investigate intestinal permeability in type I diabetes mellitus patients with no concomitant celiac disease, with a comparison to ultra-structural aspects of duodenal mucosa. PATIENTS: 46 insulin dependent diabetes mellitus, non-celiac, patients (18 females and 28 males, mean age 15.8 +/- 5.3 [S.D.] years) were enrolled. The mean duration of the disease was 5.7 years. METHODS: The morphological aspect of the small bowel mucosa, at standard light microscopy and electron transmission microscopy, along with intestinal permeability (by lactulose/mannitol test) were studied. Lactulose and mannitol urinary excretion were determined by means of high performance anion exchange chromatography-pulsed amperometric detection. RESULTS: The lactulose/mannitol ratio was 0.038 [0.005-0.176] (median and range) in 46 patients compared to 0.014 [0.004-0.027] in 23 controls: insulin dependent diabetes mellitus group values being significantly higher than those of the controls (P < 0.0001, Mann-Whitney test). Eight insulin dependent diabetes mellitus patients underwent endoscopy and biopsies were analysed by means of light microscopy and transmission electron microscopy. At the light microscopy level, none of the biopsy samples showed any sign of atrophy nor inflammation, whereas transmission electron microscopy analysis showed remarkable ultra-structural changes in six out of the eight patients. Four parameters were evaluated: height and thickness of microvilli, space between microvilli and thickness of tight junctions. CONCLUSIONS: This alteration of intestinal barrier function in non-celiac type I diabetes mellitus, frequently associated with mucosal ultra-structural alterations, could suggest that a loss of intestinal barrier function can be a pathogenetic factor in a subset of insulin dependent diabetes mellitus patients.

The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine.

Endoluminal release of serotonin (5-HT), substance P (SP), and motilin was quantitated after thoracic vagal nerve stimulation in the cat. In duodenum and jejunum, simultaneous release of these compounds was observed. In contrast, vagal stimulation did not augment the rate of luminal secretion of either 5-HT or SP in the distal ileum. Immunohistochemical studies demonstrated 5-HT in both enterochromaffin (EC) cells and nerves throughout the small bowel. However, we were unable to visualize any SP-containing EC cells in the cat, which suggests that the source of luminal SP in this species must be intramural nerves.

Effect of cervical and thoracic vagal stimulation on luminal serotonin release and regional blood flow in cats.

In acute experiments on 14 cats, the transected vagus nerves were stimulated at two levels (10 V, 5 ms, 10 Hz, 10 mA, 15 min). Fifteen-centimeter proximal jejunal segments were perfused with saline (1.0 ml/min). Basal luminal immunoreactive serotonin secretion averaged 206 +/- 67 ng/5 min. After stimulation of the vagus nerves, there was an immediate two- to threefold increase in the rate of secretion of immunoreactive serotonin into the lumen. There were no significant differences in the stimulated secretory rates that resulted from stimulation at the cervical or thoracic levels. Shortly after cessation of vagal stimulation, immunoreactive serotonin secretory rates returned to basal. Vagal nerve stimulation did not result in any change in peripheral or portal venous blood concentrations of serotonin. In 12 additional cats, the effects of stimulation of the vagus nerves at the cervical and thoracic levels on regional blood flow, as determined using the microsphere technique, were compared. Cervical vagal stimulation resulted in hypotension, bradycardia, decreased perfusion of the heart, kidney, and small and large bowels, but preservation of the perfusion of the fundus and antrum. In contrast, stimulation of the transected nerves in the chest stimulated gastric blood flow but did not alter either flow to other viscera or central hemodynamics.

Release of immunoreactive serotonin into the lumen of the feline gut in response to vagal nerve stimulation.

Immunoreactive serotonin was detected in the lumen of the proximal jejunum of food-deprived cats. During perfusion of this intestinal segment in vivo, there was a constant basal rate of intraluminal secretion of this amine. The rate of secretion was significantly increased during efferent electrical stimulation of the cut cervical vagal nerves. This stimulatory effect was not altered after bilateral adrenalectomy was performed in the same animals. A synchronous release of substance P into the gut lumen was also demonstrated during vagal stimulation. During the period of increased intraluminal secretion of immunoreactive serotonin, there was no demonstrable change in the portal or systemic blood levels of this amine.