sincalide and Atrophy

The aim of this study was to evaluate the concept that pancreatic dysfunction in patients having gluten sensitivity (celiac disease [CD]) or cow's milk protein enteropathy (CMPE) may result from the lack of pancreatic enzyme stimulation in the absence or decrease of cholecystokinin (CCK) secretion caused by villous atrophy.. The following parameters were measured: plasma CCK in response to a fatty meal and human pancreatic fecal elastase in 24 patients with CD while on gluten-free diet and after gluten provocation and in 12 patients with CMPE at diagnosis and after a 6-month period of cow's milk-free diet. Intestinal mucosa morphology was examined by small bowel biopsy. Sixty-three controls having no organic gastrointestinal problems were investigated once at the time of diagnostic evaluation.. Fasting CCK, obtained at a time when patients with CD or CMPE had normal intestinal mucosa, was significantly different from postprandial and comparable to that of the control group. Fasting CCK obtained from patients with villous atrophy was also statistically different, but not significantly, from the postprandial. Fasting and postprandial plasma CCK and fecal pancreatic elastase values from patients having normal intestinal mucosa were significantly higher than those obtained from patients with villous atrophy. Significant correlation of intestinal mucosa morphology and CCK with fecal elastase concentration was documented.. Exocrine pancreatic dysfunction in individuals having villous atrophy may be the consequence of decreased CCK secretion. Cholecystokinin and pancreatic secretion is restored to normal, with intestinal mucosa regeneration.

Topics: Adolescent; Atrophy; Biopsy; Celiac Disease; Child; Child, Preschool; Cholecystokinin; Dietary Fats; Feces; Female; Humans; Infant; Intestinal Mucosa; Intestines; Male; Milk Hypersensitivity; Milk Proteins; Pancreas; Pancreatic Elastase; Sincalide

Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.

Topics: Animals; Atrophy; Chromaffin Cells; Chromogranin A; Chromogranins; DNA Probes; Gastric Mucosa; Gastrins; Gene Expression; Genomic Library; H(+)-K(+)-Exchanging ATPase; Histidine Decarboxylase; Homozygote; Humans; Hypertrophy; Mice; Mice, Knockout; Omeprazole; Parietal Cells, Gastric; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Signal Transduction; Sincalide

The morphology and function islets isolated from rat pancreases with short-term (16 days) exocrine atrophy was investigated. It was found that this type of atrophy induced changes in the shape and morphological structure of pancreatic islets. However, the function of isolate islets did not change, as investigated by the basal or glucose-stimulated secretion of insulin, glucagon and somatostatin, and by the CCK-stimulated secretion of insulin. We conclude that the rat pancreas brought to atrophy by a short-term ligation of the pancreatic duct can be considered as a rich source of functionally viable islets.

Topics: Animals; Atrophy; Glucagon; Glucose; Insulin; Insulin Secretion; Islets of Langerhans; Ligation; Male; Pancreas; Rats; Rats, Inbred Strains; Sincalide; Somatostatin