oxyntomodulin and Celiac-Disease

Topics: Animals; Blood Glucose; Celiac Disease; Digestive System; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Ileum; Insulin; Intestine, Small; Islets of Langerhans; Jejunum; Peptide Fragments; Peptides; Vagotomy

Coeliac disease is a common chronic inflammatory enteropathy characterized by villous atrophy and crypt hyperplasia in the small intestine. The mechanism of the intestinal damage in coeliac disease remains unclear. Glucagon-like peptide (GLP)-2 is an enterotrophic peptide that causes crypt hyperplasia and intestinal cell proliferation. We postulate that GLP-2 may be involved in the mucosal changes found in coeliac disease.. To study plasma concentrations of GLP-2 in untreated patients with coeliac disease and determine the response to a gluten-free diet (GFD).. A 440 kcal gluten-free test meal was given to seven controls and 12 coeliac patients at three time intervals: (1) before commencing a GFD; (2) 3 months after a GFD; and (3) 9 months after a GFD. Serial blood sampling was performed over a 2-h period. Each sample was analysed using radioimmunoassay for GLP-2, GLP-1, N-terminal glucagon (N-glucagon) and C-terminal glucagon (C-glucagon).. Untreated coeliac patients had significantly higher basal and peak GLP-2 and N-glucagon plasma concentrations compared with controls. After 3 months on a GFD, there was a significant decrease in basal GLP-2 plasma concentrations. There was no significant difference between GLP-1 or C-glucagon in untreated coeliac patients compared with controls.. This is the first reported study of GLP-2 in coeliac disease. After a GFD there is recovery of the intestine and a reduction in the GLP-2 trophic response. Our findings support the theory that GLP-2 may be part of the mucosal healing and maintenance mechanisms in coeliac disease.

Topics: Adult; Celiac Disease; Female; Follow-Up Studies; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Glutens; Humans; Male; Middle Aged; Radioimmunoassay; Treatment Outcome

The aim of the study was to evaluate the new hormonal entity oxyntomodulin-like immunoreactivity in malabsorption states, and to assess its potential in celiac disease management.. We measured basal and postprandial oxyntomodulin-like immunoreactivity values in 35 children divided into 3 groups: group 1 was composed of 13 children with celiac disease, either under a gluten-free diet (8 patients) or normal diet (5 patients); group 2 was composed of 8 children hospitalized for gastroenteritis or chronic diarrhea, without biological evidence of malabsorption nor abnormal jejunal mucosa; group 3 was composed of 22 control subjects.. Fasting and meal-stimulated levels in the control group were 71+/-10 and 130+/-26 pmol/l, respectively. Mean concentrations were elevated in patients with celiac disease (basal = 349+/-254 pmol/l, postprandial = 446+/-332 pmol/l) and in the group 2 (basal = 139+/-58 pmol/l, postprandial = 218+/-85 pmol/l), but the difference with control subjects did not reach statistical significance. In children with celiac disease, basal and stimulated values correlated with the degree of malabsorption as assessed by hemoglobin (p = 0.006 and p = 0.01, respectively) and serum folate concentrations (p = 0.03 and p = 0.02, respectively).. Oxyntomodulin-like immunoreactivity is noticeably higher in healthy children than previously measured in healthy adult subjects. This hormonal parameter is not an adequate diagnostic tool in celiac disease. Nevertheless, in the context of celiac disease, its elevation reflects the degree of malabsorption and may provide a quantitative approach of the extent of mucosal damage.

Topics: Biomarkers; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Fasting; Female; Glucagon-Like Peptides; Humans; Male; Oxyntomodulin; Postprandial Period; Prospective Studies; Radioimmunoassay

Topics: Celiac Disease; Dumping Syndrome; Gastrointestinal Hormones; Glucagon-Like Peptides; Glucose; Humans; Radioimmunoassay

Necrolytic migratory erythema is the distinctive skin rash of the glucagonoma syndrome. Its presence is virtually pathognomonic of a glucagon-producing pancreatic islet cell neoplasm. Results of a study of a patient with hyperglucagonemia and necrolytic migratory erythema complicating untreated celiac disease are reported. Whereas pancreatic glucagon was only mildly elevated, there was marked elevation of enteroglucagon. Immunofluorescence staining demonstrated numerous (19.6 cells per square millimeter of mucosa) enteroglucagon-positive small intestinal crypt cells. Treatment with gluten-free diet not only resulted in resolution of malabsorption and improvement in small intestinal histology but was paralleled by disappearance of necrolytic migratory erythema, normalization of plasma glucagon levels, and marked reduction in the number of enteroglucagon-producing crypt cells (0.2/mm2 mucosa). The findings demonstrate that necrolytic migratory erythema is not an exclusively paraneoplastic phenomenon and that it can occur in association with excess production of enteroglucagon by the intestinal mucosa.

Topics: Celiac Disease; Erythema; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Immunohistochemistry; Intestinal Mucosa; Intestine, Small; Male; Middle Aged; Necrosis

To study whether or not plasma enteroglucagon reflects changes of the small intestinal mucosa during different phases of celiac disease, we studied fasting and postprandial concentrations of plasma enteroglucagon, as well as small intestinal mucosa morphology, in children with celiac disease and in a reference group of children without gastrointestinal disorders. The children with celiac disease were studied before dietary treatment, during gluten-free diet, and during gluten challenge. In untreated celiac children we found high mean basal and postprandial plasma enteroglucagon concentrations compared with the reference group (p less than 0.001). After a gluten-free diet period of 0.2-4.5 years (mean, 1.0 year), when the small intestinal histology was normal or only mildly abnormal, there was a decrease of both mean basal plasma enteroglucagon concentration (from 81 to 17 pmol/L; p less than 0.001) and mean postprandial plasma enteroglucagon concentration (from 129 to 39 pmol/L; p less than 0.001). During a subsequent gluten challenge, which resulted in a mucosal relapse, there was a rise in mean postprandial plasma enteroglucagon concentration (from 39 to 74 pmol/L; p less than 0.005), although there was a substantial overlap in values from treated and challenged patients. These findings suggest that plasma enteroglucagon levels, particularly after a mixed meal, are correlated with the small intestinal mucosal morphology in childhood celiac disease. Determination of plasma enteroglucagon may facilitate the control of the dietary adherence during gluten-free diet and may in some children indicate mucosal relapse during gluten challenge. Thus, the number of control biopsies may be reduced.

Topics: Adolescent; Biopsy; Celiac Disease; Child; Child, Preschool; Duodenum; Eating; Fasting; Female; Gastrointestinal Hormones; Glucagon-Like Peptides; Glutens; Humans; Infant; Intestinal Mucosa; Jejunum; Male; Radioimmunoassay

Topics: Celiac Disease; Child; Female; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Jejunum; Male

To evaluate the plasma enteroglucagon assay as a test for the detection of celiac disease, we have determined basal and postprandial concentrations of enteroglucagon in plasma of children who underwent small-intestinal biopsy because of suspected celiac disease. In the 14 children with untreated celiac disease both basal [81 (SD 33) pmol/L] and postprandial [129 (SD 26) pmol/L] concentrations of enteroglucagon were significantly higher (p less than 0.001) than in the 45 children with other gastrointestinal disorders [24 (SD 9) pmol/L, and 50 (SD 22) pmol/L, respectively] and in the 15 children without gastrointestinal disorders [14 (SD 10) pmol/L, and 35 (SD 8) pmol/L, respectively]. All children with celiac disease had either basal or postprandial plasma enteroglucagon concentrations exceeding the mean + 2 SD of the results for the children with other gastrointestinal disorders. Eight of 10 children with celiac disease in whom both concentrations were measured had increased values for both. In our study the sensitivity for detection of celiac disease was 100% and the specificity 97%. Evidently determination of plasma enteroglucagon concentration is effective in diagnosing celiac disease, thereby improving the selection of patients for small-intestinal biopsy.

Topics: Adolescent; Biopsy; Celiac Disease; Child; Child, Preschool; Female; Gastrointestinal Hormones; Glucagon-Like Peptides; Glutens; Humans; Infant; Intestine, Small; Male; Probability

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.

Topics: Adult; Celiac Disease; Female; Gastrointestinal Motility; Glucagon-Like Peptides; Humans; Ileum; Jejunum; Male; Manometry; Neurotensin; Perfusion; Triglycerides

Plasma enteroglucagon was measured before and during three hours after a standard meal in 21 untreated adult patients with suspected coeliac disease who all had villous atrophy of the small intestinal mucosa and malabsorption, and in nine control subjects. In 11 of these patients the diagnosis of coeliac disease was confirmed and 10 were again investigated on a gluten free diet. The coeliac patients had higher basal (37 +/- 9 pmol/l, mean +/- SE, p less than 0.05) and postprandial (70 +/- 9 pmol/l, p less than 0.005) mean plasma enteroglucagon concentrations than the control subjects (basal 14 +/- 4 pmol/l, postprandial 25 +/- 5 pmol/l). The 10 coeliac patients on gluten free diet for five to 20 months had a basal mean plasma enteroglucagon concentration not significantly lower than before treatment (25 +/- 5 pmol/l) but significantly lower postprandial enteroglucagon concentrations than before treatment (40 +/- 7 pmol/l, p less than 0.025). Postprandial plasma enteroglucagon concentration after 90 minutes in untreated patients correlated positively to the faecal fat excretion (r = 0.58, p less than 0.02). It correlated negatively to the urinary five hour D-xylose excretion after an oral load of 165 mmol D-xylose (r = -0.71, p less than 0.01). Thus, the postprandial plasma enteroglucagon concentrations in untreated coeliac disease were related to the degree of malabsorption and they normalised during treatment with a gluten free diet.

Topics: Adult; Aged; Celiac Disease; Fasting; Female; Gastrointestinal Hormones; Glucagon-Like Peptides; Glutens; Humans; Intestinal Absorption; Male; Middle Aged

A means of estimating human enteroglucagon (glucagon-like immunoreactivity of intestinal origin) in tissues and plasma is described, based on the subtraction of RIA values obtained with the C-terminal-directed glucagon antiserum RCS5 from the total glucagon-like immunoreactivity determined with the N-terminal- to midmolecule-directed glucagon antiserum R59. Gel filtration on Sephadex G-50 of human plasma and extracts of normal human intestine separated the R59 immunoreactivity into three peaks: a small peak of void volume material, a major peak coeluting with porcine glicentin, and a smaller peak coeluting with pancreatic glucagon. No RCS5 immunoreactivity was detected in the human gut, except for a small amount constituting less than 2% of the total glucagon-like immunoreactivity in the ileum and rectum only. In extracts of human pancreas, the chromatographic profiles obtained with RCS5 and R59 assays differed from the intestinal patterns, but were identical to each other, giving no evidence of a significant amount of pancreatic R59 immunoreactivity that was not also reactive with RCS5. Chromatography of plasmas from healthy subjects and patients with dumping syndrome, active coeliac disease, and tropical sprue showed that only the second major peak of R59 immunoreactivity reflected the basal or postnutrient increases in the plasma enteroglucagon concentration. In patients with exaggerated enteroglucagon release, the rise was again found to be entirely due to an increase in this peak of immunoreactivity. This major molecular form of human enteroglucagon, similar in size to porcine glicentin, is, thus, the form most likely to be of physiological and pathophysiological significance.

Topics: Adult; Celiac Disease; Chromatography, Gel; Digestive System; Dumping Syndrome; Female; Food; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Immune Sera; Male; Middle Aged; Pancreas; Radioimmunoassay; Sprue, Tropical; Tissue Distribution

Eight patients with biopsy-verified coeliac disease were investigated after remission on a gluten-free diet. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion (IVGI) giving the same plasma glucose profile as the OGTT were carried out. The relation between gastric inhibitory polypeptide (GIP) plasma levels after oral glucose and the insulin release during OGTT and IVGI were studied. Plasma GIP concentration in the fasting state and the increase in plasma GIP during OGTT were significantly lower than in a group of eight healthy volunteers. However, the insulin potentiation during OGTT, the incretin effect, was normal. The results indicate the existence of other incretins than GIP. These are probably released from the distal small bowel in patients with coeliac disease.

Topics: Adult; Blood Glucose; Celiac Disease; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Peptide Fragments; Peptides

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).

Topics: Adolescent; Blood Glucose; Celiac Disease; Child; Child, Preschool; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Glutens; Humans; Insulin; Peptides

In adult coeliac sprue patients, intraduodenal instillation of a hypertonic glucose-citric acid solution may release gastrointestinal hormones of the proximal (secretin, gastric inhibitory polypeptide, motilin) and distal (enteroglucagon, neurotensin) small intestine and, indirectly, of the pancreas (glucagon, insulin, pancreatic polypeptide). Characteristic plasma hormone profiles can be measured radioimmunologically. The reduced secretin response reflects most sensitively the impaired function of the small intestine. Exposure of the distal small bowel to greater nutrient loads leads to markedly and constantly elevated plasma levels of enteroglucagon. Only after complete functional as well as morphologic mucosal restoration, the increased enteroglucagon concentrations return to normal. On the other hand, the neurotensin response, which is likewise enhanced in active coeliac sprue, is sooner corrected during treatment. Gastrointestinal hormones with predominantly neurocrine action, such as vasoactive intestinal peptide (VIP), are apparently less affected by coeliac sprue. Pancreatic hormones are involved in the pathophysiology of sprue only indirectly, e. g. via diminished glucose absorption.

Topics: Adult; Blood Glucose; Celiac Disease; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Secretin; Vasoactive Intestinal Peptide

Topics: Brain; Celiac Disease; Digestive System Physiological Phenomena; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Obesity; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Somatostatin; Substance P

Patients with coeliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.

Topics: Adolescent; Adult; Aged; Blood Glucose; Celiac Disease; Child; Child, Preschool; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Infant; Insulin; Insulin Secretion; Intestine, Large; Intestine, Small; Male; Middle Aged; Secretin