Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon.

BACKGROUND: Mucins play an important protective role in the colonic mucosa. Luminal factors modulating colonic mucus release have been not fully identified. AIM: To determine the effect of some dietary compounds on mucus discharge in rat colon. METHODS: An isolated vascularly perfused rat colon model was used. Mucus secretion was induced by a variety of luminal factors administered as a bolus of 1 ml for 30 minutes in the colonic loop. Mucin release was evaluated using a sandwich enzyme linked immunosorbent assay supported by histological analysis. RESULTS: The three dietary fibres tested in this study (pectin, gum arabic, and cellulose) did not provoke mucus secretion. Luminal administration of sodium alginate (an algal polysaccharide used as a food additive) or ulvan (a sulphated algal polymer) induced a dose dependent increase in mucin discharge over the concentration range 1-25 mg/l (p<0.05 for 25 mg/l alginate and p<0.05 for 10 and 25 mg/l ulvan). Glucuronic acid and galacturonic acid, which are major constituents of a variety of fibres, produced significant mucin secretion (p<0.05). Hydrogen sulphide and mercaptoacetate, two sulphides produced in the colonic lumen by microbial fermentation of sulphated polysaccharides, did not modify mucin secretion. Among the short chain fatty acids, acetate (5-100 mM) induced a dose dependent release of mucus (p<0.05 for 100 mM acetate). Interestingly, butyrate at a concentration of 5 mM produced colonic mucin secretion (p<0.05), but increasing its concentration to 100 mM provoked a gradual decrease in mucus discharge. Propionate (5-100 mM) did not induce mucin release. Several dietary phenolic compounds (quercetin, epicatechin, resveratrol) did not provoke mucus discharge. CONCLUSIONS: Two algal polysaccharides (alginate and ulvan), two uronic acids (glucuronic acid and galacturonic acid), and the short chain fatty acids acetate and butyrate induce mucin secretion in rat colon. Taken together, these data suggest that some food constituents and their fermentation products may regulate the secretory function of colonic goblet cells.

Luminal peptide YY-releasing factors in the isolated vascularly perfused rat colon.

Peptide YY (PYY) is produced in endocrine L cells primarily localized in the distal bowel. These open-type L cells make contact with the intestinal chyme which may thus affect their secretory activity. The aim of the present study was to examine a large variety of luminal compounds found in colonic contents for their potential as PYY-releasing factors, using the isolated vascularly perfused rat colon. The release of PYY into the portal effluent was measured by a specific RIA. Luminal administration of 5 mM glucose or 0.5% (w/v) starch for 30 min did not induce significant release of PYY. Oleic acid (10 and 100 mM) also did not significantly increase PYY secretion. A pharmacological concentration of glucose (250 mM) and a mixture of amino acids (total concentration 250 mM) both induced PYY secretion (200% of basal). Pectin, a poly-galacturonic acid, evoked dose-dependent secretion of PYY-like immunoreactivity over the range 0.1-0.5% (w/v). The maximal response was observed after infusion of 0.5% pectin which induced a prompt and sustained release of PYY (300% of basal). Galacturonic acid itself (5%) produced marked PYY secretion. Gum arabic (0.5%) induced a gradual increase in portal PYY concentration (maximal response 250% of the basal value) whereas cellulose (0.5%) did not elicit PYY secretion. Luminal n-butyrate over the range 0.5-5 mM produced a dose-dependent release of PYY (maximal response 300% of the basal value with 5 mM n-butyrate). Increasing the concentration of n-butyrate to 100 mM provoked a gradual decrease in PYY secretion. Propionate was a less potent stimulant than n-butyrate, and acetate did not increase PYY secretion above the basal value. At a concentration of 2 or 20 mM, taurocholate, cholate and deoxycholate brought about PYY secretion while hyodeoxycholate was without effect. In conclusion, glucose and amino acids may mediate PYY release but only when they are present at high supraphysiological concentrations in the colon while oleic acid does not produce any PYY secretion. Physiological concentrations of fibers (pectin, gum arabic), short-chain fatty acids (n-butyrate, propionate) and bile salts (taurocholate, cholate, deoxycholate) are all potent stimulants of PYY release. Whether the release of PYY by luminal factors is coupled to water and electrolyte transfer via a local/paracrine pathway remains an open question which requires additional work with the isolated vascularly perfused colon preparation.

Luminal glucagon-like peptide-1(7-36) amide-releasing factors in the isolated vascularly perfused rat colon.

Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of the distal part of the gut after ingestion of a meal. GLP-1 secretion is, in part, under the control of hormonal and/or neural mechanisms. However, stimulation of the colonic L cells may also occur directly by the luminal contents. This was examined in the present study, using an isolated vascularly perfused rat colon. GLP-1 immunoreactivity was measured in the portal effluent after luminal infusion of a variety of compounds which are found in colonic contents (nutrients, fibers, bile acids, short-chain fatty acids (SCFAs)). Oleic acid (100 mM) or a mixture of amino acids (total concentration 250 mM), or starch (0.5%, w/v) did not increase GLP-1 secretion over basal value. A pharmacological concentration of glucose (250 mM) elicited a marked release of GLP-1 which was maximal at the end of infusion (400% of basal), while 5 mM glucose was without effect on secretion. Pectin evoked a dose-dependent release of GLP-1 over the range 0.1-0.5% (w/v) with a maximal response at 360% of basal when 0.5% pectin was infused. Cellulose or gum arabic (0.5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or butyrate (5, 20 and 100 mM) did not induce a significant release of GLP-1. Among the four bile acids tested, namely taurocholate, cholate, deoxycholate and hyodeoxycholate, the last one was the most potent at eliciting a GLP-1 response with a maximal release at 300% and 400% of the basal value when 2 and 20 mM bile acid were administered respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Food-dependent Cushing's syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide.

BACKGROUND: Some patients with Cushing's syndrome have nodular adrenal hyperplasia. In most the disease is corticotropin-dependent, but in others it is corticotropin-independent. The cause of the adrenal hyperplasia in the latter patients is not known. METHODS: We studied a 49-year-old woman with Cushing's syndrome and nodular adrenal hyperplasia in whom food stimulated cortisol secretion. Plasma cortisol concentrations were measured in response to the ingestion of mixed meals, glucose, protein, and fat and after the administration of various gastrointestinal and other types of hormones. We also studied the ability of the long-acting somatostatin analogue octreotide to prevent the food-induced increase in plasma cortisol concentrations and to ameliorate the clinical manifestations of Cushing's syndrome in this patient. RESULTS: The patient's fasting plasma cortisol concentrations were subnormal, ranging from 3.0 to 7.5 micrograms per deciliter (83 to 207 nmol per liter), and they increased to as high as 16.5 micrograms per deciliter (455 nmol per liter) after a mixed meal. Her urinary cortisol excretion ranged from 164 to 250 micrograms per day (453 to 690 nmol per day) and could not be suppressed by a large dose of dexamethasone. Plasma corticotropin concentrations were virtually undetectable at all times. The ingestion of glucose, protein, and fat increased plasma cortisol concentrations to 3.6, 2.2, and 4 times the base-line value, respectively; the meal-induced and glucose-induced increases were inhibited by octreotide. The infusion of gastric inhibitory polypeptide (GIP) increased the patient's plasma cortisol concentration to 3.7 times the base-line value, but had no effect in normal subjects. The patient's fasting plasma GIP concentrations were normal both before and after a meal, and there was a close correlation between her plasma cortisol and GIP concentrations. Treatment with octreotide decreased urinary cortisol excretion and ameliorated the clinical manifestations of Cushing's syndrome. CONCLUSIONS: The development of aberrant adrenal sensitivity to GIP can result in food-dependent adrenal hyperplasia and therefore in Cushing's syndrome.

[Increase of energy expenditure in Parkinson's disease]. / Augmentation de la dépense énergétique au cours de la maladie de Parkinson.

Energy expenditure was determined in 18 patients with Parkinson's disease, 6 healthy volunteers and 6 patients with essential tremor, age-matched, using the indirect calorimetric method which measures the gas exchange rate. The results showed a significant increase in the relative energy expenditure, i.e. the difference between absolute and predictable values from the Harris and Benedict equation, among the parkinsonian patients (+21 +/- 4.1 p. 100; mean +/- S.E.M.) as compared to the 2 control groups (-8.6 +/- 7 p. 100 and -2.1 +/- 4.1 p. 100 respectively; p less than 0.001). There was no correlation between the rate of energy expenditure and the duration or degree of severity of the disease, and particularly the occurrence and magnitude of weight loss, which is frequently observed during the course of the disease. The relative energy expenditure was not significantly different between untreated and treated parkinsonian patients (18.8 +/- 3 p. 100 and 24.5 +/- 6.2 p. 100 respectively). Further investigations were designed to determine whether the increased energy expenditure could reflect a functional impairment of the automatic nervous system. The integrity of the vagus nerve was tested by plotting vs time the plasma Pancreatic Polypeptide levels in response to insulin-induced hypoglycaemia. A physiological stimulation was obtained in the 8 parkinsonian patients studied. This is not the case in chronic autonomic failure. On the contrary, the relative energy expenditure was significantly decreased in the 6 patients that were given a beta-blocking drug, pindolol, 15 mg daily for 3 weeks (+30.7 +/- 4.3 p. 100 before and +21 +/- 4.2 p. 100 after treatment; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical distribution of somatostatin in the infant hypothalamus.

Somatostatin (SS)-containing neurons were mapped in the normal infant hypothalamus with immunohistochemistry, using the peroxidase anti-peroxidase technique. Neurons displaying SS immunoreactivity show a widespread distribution throughout the hypothalamic region. Principal SS-immunoreactive like (SS-IL) perikarya are located in the paraventricular, infundibular and posterior nuclei and in the preoptic region. High SS innervation is also found in the ventromedial and in the lateral mammillary nuclei, and in the median eminence. In general this distribution of SS-IL agrees well with that reported for rat. Compared to the immunohistochemical distribution of SS in human adult hypothalamus, this mapping in the infant hypothalamus is grossly similar. However some differences may be underlined: the presence of a moderately dense group of SS-IL perikarya in the tuberal and posterior nuclei, and a dense innervation of the ventromedial nucleus and in the median eminence. This first detailed distribution of SS immunoreactivity in infant hypothalamus can provide basic knowledge for further studies of infant neuropathology.

Ontogeny of substance P in the digestive tract, spinal cord and hypothalamus of the human fetus.

The time of appearance and tissue concentrations of substance P-like immunoreactivity (SP-LI) were studied in 53 human fetuses aged 8-21 weeks. Detectable amounts were present at 8 weeks of gestation in available fragments of spinal cord and intestine. Thereafter, the tissue concentrations were highest in spinal cord, intermediate in hypothalamus and lowest in digestive tract. Except for a significant increase in the intestinal wall, the concentrations did not vary from the 8-14 to the 15-21 week period. At chromatography, SP-LI in extracts of spinal cord and intestine was essentially eluted in the volume of the synthetic undecapeptide. Using the indirect immunofluorescence technique, the localization of SP-LI positive structures in the digestive tract was studied in 5 fetuses aged 12-18 weeks. Scarce cell bodies were observed in the myenteric plexus. Nerve fibers were recognized in the muscular layer, in the myenteric plexus and in connective tissue of pancreas. The present results demonstrate the early appearance of SP-LI positive structures both in central nervous system and in the enteric nervous system in the human fetus. In the age range tested, SP-LI concentrations were noticeably higher in spinal cord and hypothalamus than in the digestive tract.

Effect of increased amounts of pectin on a solid-liquid meal digestion in healthy man.

The effect of three concentrations of high-methoxy apple pectin (5, 10, and 15 g), on solid-liquid meal digestion was studied in 12 healthy men by the gastrointestinal intubation technique. The gastric emptying of water and carbohydrates is significantly reduced only after 10 and 15 g pectin. The changes in gastric pH are similar for pectin-free and pectin-containing meals. Cumulative lipase and trypsin outputs are not significantly different with and without pectin. When gastric uronic acid concentration is above 6 g/l, the duodenal absorption of carbohydrates is significantly reduced (p less than 0.001). The mean blood glucose levels with 10 and 15 g pectin are significantly higher than the control values at 180 min (p less than 0.05). Pectin does not modify serum concentrations of secretin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and somatostatin but serum motilin and gastrin levels are below the control values after high fiber meal.

Substance P-, somatostatin-, vasoactive intestinal peptide- and cholecystokinin-like levels in the spinal cord of polyarthritic rats.

Substance P-, somatostatin-, vasoactive intestinal polypeptide- and cholecystokinin-like levels were measured in lumbar dorsal and ventral cord of polyarthritic rats and compared with those obtained in vehicle-treated rats taken as controls. Polyarthritis decreased substance P concentration in lumbar ventral cord and increased cholecystokinin level in lumbar dorsal cord, while the other two peptides did not show any change. The results are discussed in relation to immunohistochemical data found in the literature.

Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patient with pancreatic cholera.

The effects of somatostatin on diarrhea and on small intestinal flow of water and electrolytes (slow-marker perfusion technique) in a patient with pancreatic cholera are reported. Continuous intravenous infusion of somatostatin (8 micrograms/kg/hr) suppressed the diarrhea, but a rebound was observed after somatostatin. Infusion of somatostatin at the same dosage decreased the ileal fluid flow rate to within control values. This effect was mainly due to a sharp reduction in the rate fluid entered the jejunum, but was also due to a suppression of the abnormal water and electrolyte secretion in the proximal jejunum. Secretion in the rest of the small bowel remained unchanged. Somatostatin did not noticeably alter the high preinfusion plasma level of prostaglandin E1, but decreased the initially high plasma concentration of vasoactive intestinal peptide to normal values. These results suggest that long-acting somatostatin analogs could be of value in the symptomatic treatment of diarrhea in pancreatic cholera.

Effect of early oral calcium supplementation on serum calcium and immunoreactive calcitonin concentration in preterm infants.

Oral calcium supplements (80 mg/kg per 24 h) were given to 23 preterm infants, and the course of serum calcium, magnesium, immunoreactive calcitonin, and gastrin was compared with a control group of 23 matched infants. In the supplemented group, serum calcium concentrations remained at the baseline level (2.31 mmol/l +/- 0.18 SD) while a fall (from 2.27 +/- 0.18 to 1.91 +/- 0.24 mmol/l) was observed at 12-16 hours of age in the control group, with 4 values < 1.75 mmol/l. There was no change in serum magnesium concentration in either group. The postnatal rise of serum immunoreactive calcitonin concentrations in the control group (from 171 +/- 135 to 493 +/- 273 pg/ml at 12-48 hours of age) was not found in the supplemented group. There was a negative correlation between serum calcium and immunoreactive calcitonin levels in the control group, but not in the supplemented group. There was no correlation between serum immunoreactive calcitonin and gastrin concentrations. These data show that oral calcium supplementation can prevent early neonatal hypocalcaemia, and suggest that this effect is achieved at least in part through a reduction of the postnatal rise of serum immunoreactive calcitonin.

Ontogeny of somatostatin in the human gastro-intestinal tract, endocrine pancreas and hypothalamus.

The appearance, time and distribution of somatostatin in the pancreas, gastro-intestinal tract and hypothalamus were studied comparatively in human foetuses aged 6--32 weeks, by immuno-cytochemistry and radioimmunoassay. Somatostatin was detected by both methods in all segments including the colon. The first cells were observed, and somatostatin was present in measurable amounts at 8 weeks in pancreas, duodenum and intestine, while the peptide was detected at 12 weeks in antrum and colon, at 14 weeks in fundus, and at 16 weeks in hypothalamus. Subsequently, the largest cell population was located in the pancreas, where peptide concentration and age were positively correlated (P less than 0.01, r = 64). From 15 to 21 weeks of age, the mean somatostatin concentration in pancreas (12.4 +/- 1.84 ng/mg) was clearly higher than in hypothalamus (0.05 +/- 0.02 ng/mg) or in any segment of the gut, where values ranged from 0.36 +/- 0.06 (fundus) to 4.74 +/- 0.83 ng/mg (duodenum). The early appearance time of somatostatin, and its specific distribution with preferential location in the pancreas, suggest that the peptide may play a major role for the development of the foetal digestive tract, and that it may be involved in the regulation of other endocrine secretions, especially in the pancreas.