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PubMed1993

Role of growth factors in pancreatic endocrine cells. Growth and differentiation.

Although previously thought to arise from neural ectoderm, the endocrine cells of the gastrointestinal system are now believed to derive from endoderm. The role of different growth factors in initiation of endocrine cell growth, commitment of the cells to a particular growth pathway, and the initiation and maintenance of tumor growth and remission remains unclear. This article briefly reviews factors controlling cell growth and differentiation of gastrointestinal endocrine cells and presents data on new candidate growth factors pertinent to the authors' model of induction of endocrine cell differentiation in the pancreas.

Cell Differentiation↗
PubMed1994

Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signaling by the endogenous receptors of beta cell lines.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that potentiates glucose-induced insulin secretion by pancreatic beta cells. The mechanisms of interaction between GLP-1 and glucose signaling pathways are not well understood. Here we studied the coupling of the cloned GLP-1 receptor, expressed in fibroblasts or in COS cells, to intracellular second messengers and compared this signaling with that of the endogenous receptor expressed in insulinoma cell lines. Binding of GLP-1 to the cloned receptor stimulated formation of cAMP with the same dose dependence and similar kinetics, compared with the endogenous receptor of insulinoma cells. Compared with forskolin-induced cAMP accumulation, that induced by GLP-1 proceeded with the same initial kinetics but rapidly reached a plateau, suggesting fast desensitization of the receptor. Coupling to the phospholipase C pathway was assessed by measuring inositol phosphate production and variations in the intracellular calcium concentration. No GLP-1-induced production of inositol phosphates could be measured in the different cell types studied. A rise in the intracellular calcium concentration was nevertheless observed in transfected COS cells but was much smaller than that observed in response to norepinephrine in cells also expressing the alpha 1B-adrenergic receptor. Importantly, no such increase in the intracellular calcium concentration could be observed in transfected fibroblasts or insulinoma cells, which, however, responded well to thrombin or carbachol, respectively. Together, our data show that interaction between GLP-1 and glucose signaling pathways in beta cells may be mediated uniquely by an increase in the intracellular cAMP concentration, with the consequent activation of protein kinase A and phosphorylation of elements of the glucose-sensing apparatus or of the insulin granule exocytic machinery.

Animals↗
PubMed1993

[Pouchitis: acute inflammation in the pelvic ileal reservoir. Diagnostic criteria, frequency, possible etiological factors and treatment].

Pouchitis is a significant long-term complication of restorative proctocolectomy. Pouchitis is characterized by diarrhoea, fever, malaise, abdominal pain and in few a patients a worsening of already present extraintestinal manifestations may occur. The estimated probability of pouchitis occurring within five years is approximately 35%. Standard diagnostic criteria have not yet been established, but clinical symptoms, endoscopic and histological features should be included. The cause of pouchitis is unknown, bacterial over-growth, faecal stasis, oxygen free radicals, secondary and deconjugated bile acids, shortchain fatty acids, gastrointestinal hormones and an immunologically-mediated reaction have all been suggested as possible etiological factors. Metronidazole is the most commonly used treatment and has prompt effect in more than 90% of the patients. Steroids and 5-aminosalicylic acid derivatives also seem to be effective. A diverting ileostomy is necessary in only five to seven percent of the patients, and in less than one percent does pouchitis result in excision of the pouch. Controlled trials with uniform diagnostic criteria are required to assess the effectiveness of the individual regimens.

Acute Disease↗
PubMed1993

Epidermal growth factor limits structural alterations in gastrointestinal tissues and decreases bacterial translocation in burned mice.

BACKGROUND: Burn injury produces acute gastrointestinal derangements that may predispose to bacterial translocation (BT). We studied effects of recombinant human epidermal growth factor (r-HuEGF), a gastrointestinal trophic hormone, on gastrointestinal alterations and BT after murine burn injury. METHODS: r-HuEGF was administered 1 and 12 hours after burn injury in a dose of 4 micrograms per animal subcutaneously after 25% and 32% total body surface area (TBSA) scald burn. Small bowel and gastric weight and histologic factors were studied, and BT was measured by culturing mesenteric lymph nodes. RESULTS: Mice treated with r-HuEGF maintained gastric and small intestine weight measured 24 hours after burn injury, and ileal mucosal height was preserved, whereas burned-untreated mice lost organ weight and mucosal height. BT was decreased significantly in mice with 32% TBSA burn injury treated with r-HuEGF after injury (burn, 64.2% of animals had BT; burn-r-HuEGF, 34.6% had BT; p < 0.05). After 25% TBSA burn injury, BT was also decreased in r-HuEGF-treated animals (burn, 31.4% of animals had BT; burn-r-HuEGF, 14.3% had BT), but the difference was not statistically significant (p < 0.1). CONCLUSIONS: r-HuEGF improves intestinal and gastric structure in mice 24 hours after burn injury and decreases BT after 32% TBSA burn injury.

Absorption↗
PubMed1993

Nitric oxide inhibits the myoelectric activity of the small intestine in dogs.

Intestinal motility in fasted animals shows cyclic changes (MMC) that are interrupted by feeding. The aim of this study was to determine the possible implication of nitric oxide (NO) (that was proposed as nonadrenergic noncholinergic neurotransmitter) in the motor components of MMC in 5 conscious dogs equipped with monopolar electrodes implanted along the small bowel. In fasted dogs with typical MMCs, L-NNA (an inhibitor of NO synthase) (5 mg/kg-h i.v.) decreased the MMC interval from control 80 +/- 7 to 60 +/- 4 min and increased significantly the spike activity. Infusion of L-arginine (L-Arg) (a substrate of NO synthase) (10 mg/kg-h i.v.) increased the MMC interval from control 79 +/- 7 to 96 +/- 8 min and reduced the slow waves with spikes by about 25%. Similar but transient effects were observed when glycerin trinitrate (GTN) (a donor of NO) (1 mg/kg-h) was administered. After ingestion of meal, the MMC cycles were replaced by irregular spike activity with an average of about 35% slow waves with spikes. Infusion of L-Arg (10 mg/kg-h) reduced by about 90% the postprandial spike activity. Also, infusion of GTN (1 mg/kg-h) strongly reduced the postprandial spike activity. L-NNA in fed dogs caused an initial increase in spike activity followed by phase III-like activity. Similar effects were obtained when L-NNA was infused in dogs with fed-like motility patterns induced by i.v. infusion of caerulein (75 pmol/kg-h). L-NNA added to L-Arg infusion reversed in part the changes of intestinal motility patterns induced by L-Arg. We conclude that NO system exerts a tonic inhibitory influence on intestinal myoelectric activity by reducing the frequency of MMC pacesetter and by suppressing the postprandial spike activity.

Animals↗
PubMedDate not supplied

Non-radiological investigation of pancreatic disease.

Pancreatic exocrine insufficiency is investigated by long established techniques: either by duodenal intubation studies, or by indirect functional methods. Serum markers and specific gastrointestinal hormones are available for the diagnosis of pancreatic inflammation, carcinoma, and rare pancreatic endocrine tumours. The clinical utility of these diagnostic tests is discussed in this article.

Amylases↗
PubMed1996

Neuropeptide Y-related peptides and hypothalamo-pituitary-adrenal axis function.

Current data on the localization of neuropeptide Y-related peptides in the hypothalamo-pituitary-adrenal gland (HPA) axis as well as the effects of these peptides on the function of cells comprising HPA axis are presented and discussed. The action of neuropeptide Y, peptide YY, and pancreatic polypeptide on HPA axis are evaluated. Moreover, we report the presence of pancreatic polypeptide immunoreactivity in subset of chromaffin cells in the medulla of rat adrenal gland.

Adrenocorticotropic Hormone↗
PubMed1996

[Tumor imaging in nuclear medicine].

Tumor imaging in nuclear medicine has been improved by imaging instruments and newly developed radiopharmaceuticals. One of the imaging developments is a SPECT system using three-detector system. Its each detector rotates 120 degrees when SPECT projection data are acquired and we can save the scanning time and get a high resolution image which is less than 10 mm FWHM. About radiopharmaceuticals 99mTc MDP and 57Ga-citrate are used most commonly for detecting early metastatic lesions in the body. 201Tl chloride and 99mTc MIBI as used for cardiac imaging are also used for tumor detection. 111In-DTPA-D-Phe-octreotide are developed for detection of somatostatin receptor and will be used for many kinds of tumor such as small cell lung cancer, meningioma, malignant lymphoma and gastrointestinal hormone producing tumor.

Citric Acid↗
PubMed1977

The gastrointestinal myoelectric response to 13-Nle-motilin infusion during interdigestive and digestive states in the conscious dog.

Gastrointestinal myoelectric activity was studied in three conscious fasted dogs with electrodes surgically implanted in the stomach and small intestine, during separate and combined intravenous infusions of 13-norleucine motilin (13-nle-motilin) and pentagastrin (PG). Basal recordings confirmed the presence of regular interdigestive myoelectric complexes (MC's). 13-nle-motilin infusion below 50 ng/kg-h was without effect: higher doses up to 400 ng/kg-h resulted in the interpolation of one or more MC's in the spontaneous sequence. The rate of aboral transit of 13-nle-molitin-induced MC's did not differ significantly from that of spontaneous MC's. When MC's were abolished by feeding or PG infusion, simultaneous 13-nle-motilin administration was without effect on spike activity, but slightly attenuated the accelerating effect of gastrin on the gastric pacemaker frequency. The myoelectric events triggered by 13-nle-motilin suggest that in the conscious dog the polypeptide may not act directly on the smooth muscle cell, as it does in vitro, but through an extra-enteric neural control mechanism which is uncoupled by gastrin.

Aminocaproates↗
PubMed1997

[Effects of peptide YY on functions of the gastrointestinal tract].

The present report gives a review about the localization, release and gastrointestinal actions of peptide YY in different animal species and in humans. Possible mechanisms of action, the physiological and pathophysiological significance of peptide YY and the role of peptide YY 3-36 are discussed. Finally, unanswered questions are specified.

Amino Acid Sequence↗
PubMed1976

Clearance rate, half-life, and secretory potency of human gastrin-17-I in different species.

The clearance rates of synthetic human gastrin-17-I were measured in man, dog, and cat. Half-life of disappearance and acid secretory potency (D50) were also measured in man and dog. The clearance rates in dog and cat were, respectively, 3 and 8 times more than in man. Accordingly, the half-life of gastrin-17 in the dog (3.5 min) was 3 times shorter than in man (9.5 to 10.5 min). The D50 for acid secretion was proportional to the clearance rate and yielded approximately similar increments of serum gastrin, indicating an equal sensitivty to gastrin-17 at cellular level in the three species. An inverse allometric relation between clearance rate and body weight was consistent with the known greater efficiency of metabolic and eliminatory processes in species of small size. Recent studies of the disposal of other gastrointestinal hormones indicate that the concepts developed theoretically for secretory stimulants and confirmed experimentally for gastrin-17 may have wider applicability.

Animals↗
PubMed1997

Dose depending effect of the complex action hemocorrector "Lactosorbal" on the motility of the distal colon in the paralitic ileus dogs.

For the model of paralytic ileus caused by the severe surgery it has been studied the influence of different doses of hemocorrector of "Lactosorbal" on distal colon motility. It has been established that stimulating effect of "Lactosorbal" on the motility of distal colon is of the dose-dependent nature. The results of the current survey are making the ground for multiple use of "Lactosorbal" to reach the most beneficial outcome of severe paralytic ileus resulting from major traumatic surgery in clinic.

Animals↗
PubMed1976

Characterization of a hyperactive segment at the rectosigmoid junction.

During a study of intraluminal motor patterns of the colon and rectum, spontaneous wave activity of a continuous complex type was observed at the rectosigmoid junction in constipated subjects. To assess the frequency and characteristics of this hyperactive segment, 36 subjects with colonic motor disorders and 12 healthy controls were studied. Eighteen of 24 patients with constipation (75%) and 1 of 7 subjects with asymptomatic diverticulosis exhibited a persistent hyperactive segment at the rectosigmoid junction. Neither secretin nor cholecystokinin influenced the wave activity of the hyperactive segment. In contrast, atropine and glucagon inhibited markedly all wave activity and decreased the motility index of this segment significantly, suggesting overactivity of the muscarinic effector cells. It is concluded that a segmental area of overactivity exists at the rectosigmoid junction in most constipated subjects regardless of their underlying disorders.

Adult↗
PubMedDate not supplied

Endogenous motilin and lower esophageal sphincter pressure in man: clue to an association.

In man (n = 5), after intraduodenal instillation of 50 ml of 0.1 N hydrochloric acid the lower esophageal sphincter pressure (LESP) and plasma motilin concentrations rise concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. These results suggest that the increase in LESP after duodenal acidification may be brought about by endogenously released motilin.

Adult↗