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Intestinal very low density lipoprotein secretion in rats fed various amounts of fat.

1. The effect of a high-fat diet (30% fat by wt.) on intestinal very low density lipoprotein (VLDL) secretion was studied in male rats after specific inhibition of hepatic VLDL secretion by dietary orotic acid. Total VLDL secretion (from liver and intestine) was measured in animals not receiving orotic acid. 2. Fat-feeding resulted in a 32% decreased post-Triton secretion of total serum VLDL triacylglycerols as compared to a control (low fat) diet. Concomitantly, a large stimulation of post-Triton intestinal VLDL triacylglycerols secretion was measured in fat-fed rats. Thus, the major part (64%) of circulating triacylglycerols transported as VLDL originated from the intestine in these animals, leading presumably to an increased secretion of intestinal apolipoproteins. 3. Intestinal VLDL and chylomicron secretion rates increased with the amount of fat in the diet (7, 13, 20 or 30% fat by wt.). Whereas the chylomicron secretion was linearly related to the dietary fat content, the relationship between intestinal VLDL secretion and fat content of the diet was sigmoidal. The highest stimulation of intestinal VLDL formation was observed within a narrow range of dietary fat content (between 10 and 20%).

Animals↗

Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls.

Spontaneous IgG and IgG subclass secretion patterns by isolated intestinal mononuclear cells (MNC) from control and inflammatory bowel disease (IBD) specimens were examined. Intestinal MNC from IBD specimens spontaneously secreted more total IgG than did control intestinal MNC. This increased spontaneous IgG secretion by ulcerative colitis intestinal MNC was primarily due to markedly increased production of IgG1. Slightly increased secretion of IgG3, but not IgG2 by ulcerative colitis intestinal MNC was present when compared with control and Crohn's disease intestinal MNC. In contrast, Crohn's disease intestinal MNC exhibited increased spontaneous secretion of all the IgG subclasses examined, with IgG2 being predominant.

Colitis, Ulcerative↗

Changes in the chemical composition of surfactant-like particles secreted by rat small intestine in response to different dietary fats.

Consumption of dietary oil, viz., corn, fish, coconut, or olive, induced the secretion of surfactant-like particles (SLP) in rat intestine. These lipoprotein particles differ in (i) levels of alkaline phosphatase activity, (ii) lipid composition, and (iii) FA composition in response to feeding of different oils. The secreted particles had similar buoyancy (1.07-1.08 g/mL) and cholesterol/phospholipid molar ratios (0.61-0.72) except that feeding coconut oil to rats produced SLP with a low (0.18) cholesterol/phospholipid molar ratio compared to control animals. It is concluded from these observations that feeding different oils induces the secretion of lipoprotein particles in rat intestine with different chemical compositions.

Alkaline Phosphatase↗

[Methodology of investigations on the intestinal phase of gastric secretion depending on the methods for surgical treatment].

The paper presents the methodology of conducting those investigations designed to study the intestinal phase of gastric secretion, with the duodenal pH having been taken as the integral index. An acetylcholine test has been developed suggesting to us a preservation of the inhibitory duodenogastral reflex. The study into the gastric secretion in 69 patients with complications of peptic ulcer showed that the intraduodenal pH was disturbed in 39.1 percent of the patients, which fact warrants medicamentous and surgical correction to be instituted in them.

Digestive System Surgical Procedures↗

Ethanol inhibits triglyceride synthesis and secretion by human small intestinal mucosa.

We studied the effect of ethanol on human intestinal lipid absorption and on triglyceride synthesis and secretion. Human duodenojejunal biopsy specimens were incubated in a micellar lipid solution containing carbon 14-labeled oleate in the presence of ethanol 0.1%, 1.0%, and 5.0% (vol/vol). Tissue triglyceride synthesis was significantly decreased by 52.0% +/- 7.7%, 57.0% +/- 9.0%, and 81.3% +/- 4.0% (mean +/- SEM), respectively, when compared with triglyceride synthesis by control biopsy specimens incubated in the absence of ethanol. Tissue levels of oleate were increased in biopsy specimens incubated in the presence of ethanol by 90% +/- 30% and 115% +/- 5% for ethanol concentrations of 1.0% and 5.0% (vol/vol), respectively (P less than 0.02). At ethanol concentration of 0.01%, no change in tissue oleate or triglyceride levels was noted. The effect of 1.0% and 5.0% ethanol on triglyceride synthesis may reflect in large part their significant increase of the medium osmolarity. However, the osmolarity of the medium containing 0.1% ethanol was similar to that of the ethanol-free medium, and its effect is therefore probably specific. Duodenojejunal biopsy specimens were also preincubated for 30 minutes in a micellar lipid solution containing 14C-oleate, and subsequently were organ cultured in micellar-free medium in the presence or absence of ethanol 1.0% (vol/vol). During organ culture, the decrease in tissue oleate levels was similar in biopsy tissue cultured in the presence or absence of ethanol. However, in the presence of ethanol, triglyceride secretion to the organ culture medium was reduced by 49.9% +/- 11.1% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenum↗

Effect of colchicine on jejunal adenylate cyclase activity, PGE2 and cAMP contents.

The effect of colchicine on jejunal adenylate cyclase activity, prostaglandin E2 (PGE2) and cAMP contents, the enzyme and mediators involved in intestinal fluid secretion was tested in rats. Four h after the intraperitoneal injection of colchicine (0.5 mg/100 g body wt.) mucosal PGE2 content, adenylate cyclase activity and mucosal cAMP content were almost doubled. Pretreatment with indomethacin (4 mg/kg body wt., s.c./day x 2) or methyl prednisolone (3.0 mg/kg body wt.) decreased both the increase in mucosal PGE2 content and the stimulation of adenylate cyclase activity induced by colchicine. These results suggest that the stimulation of adenylate cyclase activity and an increase in mucosal PGE2 and cAMP contents might be among the mechanisms whereby colchicine induces a net accumulation of water manifested clinically as diarrhea. It is also suggested that the stimulation of adenylate cyclase activity is mediated by the increase in mucosal PGE2 content.

Adenylyl Cyclases↗

Cyclic AMP-dependent anion secretion in human small and large intestine.

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.

Adolescent↗

Development of genetically engineered human intestinal cells for regulated insulin secretion using rAAV-mediated gene transfer.

Cell-based therapies for treating insulin-dependent diabetes (IDD) can provide a more physiologic regulation of blood glucose levels in a less invasive fashion than daily insulin injections. Promising cells include intestinal enteroendocrine cells genetically engineered to secrete insulin in response to physiologic stimuli; responsiveness occurs at the exocytosis level to regulate the acute release of recombinant insulin. In this work, we established a human cellular model to demonstrate that meat hydrolysate can simultaneously stimulate glucagon-like peptide-1 (GLP-1, an enteroendocrine cell-derived incretin hormone) and recombinant insulin secretion from the engineered human NCI-H716 intestinal cell line. Cells were genetically modified using the recombinant adeno-associated virus (rAAV)-mediated insulin gene transfer. Recombinant cells were then differentiated to display endocrine features, in particular the formation of granule-like compartments. A fusion protein of insulin and enhanced green fluorescence protein (EGFP) was designed to reveal the compartments of localization of the fusion protein and assess its co-localization with endogenous GLP-1. Our work provides a unique human cellular model for regulated insulin release through genetic engineering of GLP-1-secreting intestinal cells, which is expected to be useful for cell-based therapies of IDD.

Cell Line↗

Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: mode of action and augmenting effect of inflammatory cytokines.

Oral administration of cholera toxin (CT) induces a strong mucosal immune response to CT as well as having a potent adjuvant effect. Since one of the first cell types to encounter CT during cholera infection or after oral administration is the epithelial cell, we studied the effect of CT on interleukin-6 (IL-6) secretion by the rat intestinal epithelial cell line IEC-6. CT was found to rapidly enhance IL-6 secretion and IL-6 gene expression by these cells. The addition of dibutyryl cyclic AMP (cAMP) to cultures of IEC-6 cells had little effect on IL-6 secretion, yet mRNA levels were elevated, suggesting that the response may have been regulated by cAMP. Purified B subunit of CT did not significantly enhance IL-6 secretion or mRNA expression. CT and transforming growth factor beta 1 synergistically enhanced IL-6 secretion in IEC-6 cells. The addition of CT with either IL-1 beta or tumor necrosis factor alpha gave even greater synergistic enhancement of IL-6 secretion, and dibutyryl cAMP could mimic CT's synergy with IL-1 beta. These results indicate that the intestinal epithelial cell is capable of secreting high levels of IL-6 after encountering CT, especially in the presence of inflammatory cytokines. This high level of IL-6 secretion could be a very important component of the mucosal immune response to CT and may also account for a portion of the adjuvant effect of CT.

Animals↗

[Influence of small intestine shunt and small intestine resection on gastrin secretion].

In 10 healthy controls, in 3 patients with subtotal resection of the small intestine and in 7 patients with jejuno-ileal bypass gastric ackd secretion and serum gastrin were determined in the basal state and after stimulation. The patients with short bowel revealed basal and pentagastrin stimulated gastric acid secretion in the lower normal range. Hypergastrinaemia, however, was present in these patients in the basal state and after food stimulation of gastrin release, while in patients with jejuno-ileal bypass basal and postprandial serum gastrin concentrations were within the normal range. These data suggest, that hypergastrinaemia in patients with short bowel is due to dimished gastrin catabolism and that the small intestine plays a significant role in gastrin inactivation.

Gastrins↗

Do antidiarrhoeal opiates accumulate in the rat intestinal lumen?

The opiate antidiarrhoeal drugs loperamide (0.6 mg kg-1, i.p.) or difenoxin (0.77 mg kg-1, s.c.), were administered in an anaesthetic mixture (pentobarbitone 60 mg kg-1) to rats. A length of jejunum (approx. 30 cm) was cannulated, washed and then perfused with iso-osmotic saline for 20 min. The perfusion commenced 50 min after drug administration and continued for 20 min. The perfusates were collected for analysis of fluid transport rates and antidiarrhoeal drug content. These doses of the antidiarrhoeals caused marked inhibition of intestinal fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide. However, neither of the antidiarrhoeal drugs were detected in the intestinal perfusates (< 0.5 ng by HPLC). The results indicate that loperamide and difenoxin have a different pharmacokinetic profile compared with that previously found for morphine under the same conditions.

Absorption↗

Background (spontaneous) immunoglobulin production in the murine small intestine as a function of age.

The development of the intestinal B-cell compartment in C3H/He mice was studied as a function of age by quantification of the number of intestinal immunoglobulin-secreting cells (Ig-SC). Before and at weaning, the number of Ig-SC in the small intestine (SI) was below 10(3) Ig-SC per SI. During the first few weeks after weaning, this number rose steeply and continued to rise until the mice were about 48 weeks old, when a maximum of more than 25 x 10(6) Ig-SC per SI was found. After 1 year of age the number of Ig-SC decreased. At all ages, the great majority of Ig-SC in the SI produced IgA. The increase of the number of IgA-SC in the SI after weaning is reflected in the amount of IgA in intestinal secretions measured by ELISA. The number of Ig-SC in the SI was compared with the number of Ig-SC found in spleen, bone marrow, Peyer's patches and mesenteric lymph nodes. Striking differences were observed between the SI and the other organs tested in total number, isotype distribution and kinetics of the increase of Ig-SC during ontogeny. These differences are discussed in relation to the regulation of the immune response in the SI and the migration patterns of lymphocytes in mucosal tissues.

Aging↗

Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion.

The ability of centrally administered vasoactive intestinal peptide (VIP) to stimulate PRL secretion when injected intracerebroventricularly could be due to leakage to the pituitary, where it is known to exert direct PRL-releasing activity, or to a hypothalamic action on its own release or that of another possible PRL-releasing factor. When 3 micrograms VIP were injected into the third ventricle of conscious ovariectomized rats, a significant (P less than 0.005) and transient elevation of plasma oxytocin (OT) levels was observed. When OVX rats were injected iv with 1 ml anti-OT serum 30 min before the central administration of 3 micrograms VIP, the PRL surge seen after VIP injection in normal rabbit serum-treated controls was completely absent. The PRL surge seen after central VIP administration was not significantly altered by iv saline infusion (1 ml over 30 min) or by infusion of a VIP antagonist [D-4-Cl-Phe6,Leu17]VIP at a dose of 0.5 microgram/kg.min in 1 ml saline for 30 min before the VIP injection. This was not due to the inability of the VIP antagonist to block the PRL-releasing factor activity of VIP, since it significantly antagonized that action both in vitro and in vivo in the suckling stimulation paradigm. However, the PRL surge was completely absent in ovariectomized rats pretreated by iv infusion of an OT antagonist, [deamino Cys1,D-Trp2,Val4,Orn8]OT, at a similar dose. This recruitment of OT by VIP indicates that it may act at more than one locus within the hypothalamo-pituitary axis to insure the coordinated control of PRL secretion.

Animals↗

Nutrient, neural and endocrine control of glucagon-like peptide secretion.

The intestinal glucagon-like peptides, GLP-1 and GLP-2, are important regulators of nutrient intake, digestion, absorption and metabolism. Extensive studies have shown that the co-secretion of GLP-1 and GLP-2 is regulated by a variety of dietary nutrient, neural and endocrine inputs. Furthermore, secretion of these peptides is altered in a number of pathological conditions, including type 2 diabetes and obesity. The purpose of this review is to discuss the regulation of GLP-1 and GLP-2 secretion in both health and disease.

Dietary Carbohydrates↗

Studies on the secretion of amino acids and of urea into the gastro intestinal tract of pigs. 1. Secretion of leucine into the stomach and upper part of the duodenum during continuous intravenous infusion of 14C-leucine.

Three pigs of 34 kg live weight were fitted with a re-entrant cannula in the duodenum, and with two catheters placed in the jugular vein and carotid artery. They were fed 1.2 kg/d of wheat-dried-skimmed milk diet. Digesta from the proximal duodenal cannula were collected for 12 h on 2 consecutive days; 50% were reintroduced into the respective distal cannula and 50% were stored at -20 degrees C. Three days later 14C-leucine was infused into the jugular vein for 12 h, starting with the morning meal. During this period the digesta from the proximal cannula were collected and stored for analysis while the digesta collected previously were reintroduced into the distal cannula. Blood samples were taken from the carotid artery. The total flow of duodenal digesta in 12 h was 5760 +/- 530 g. On average 70 percent of the radioactivity in digesta was associated with the TCA-precipitable fraction. During hours 0-3 and 11-12 of infusion 60-70% and 96-98% of the radioactivity in the TCA precipitable fractions was in leucine. In the TCA soluble fraction only 30-40 per cent of the radioactivity was associated with leucine. At the plateau 2.1 and 3.3% of infused 14C-leucine and of radioactivity were recovered in the duodenal digesta. The calculated amount of endogenous protein passing the duodenum was 20.4 g/d/pig. The results are discussed in relation to previous studies on protein synthesis and secretion in which 14C- and 15N-amino acids were used.

Amino Acids↗

Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins.

Clostridium difficile, the major etiologic factor of antibiotic-associated diarrhea and colitis, mediates its effects by releasing two large protein exotoxins, toxins A and B. A major toxin effect is related to the disassembly of actin microfilaments, leading to impairment of tight junctions in human colonocytes. The mechanism of actin disaggregation involves monoglucosylation of the signaling proteins Rho A, Rac, and Cdc 42, which control stress fiber formation directly by toxins A and B. An important aspect of C. difficile infection is the acute necroinflammatory changes seen in patients with pseudomembranous colitis. The early mechanism of toxin-mediated inflammation involves toxin effects on cellular mitochondria, release of reactive oxygen species, and activation of mitogen-activated protein kinases and the transcription factor nuclear factor-kappaB. Injection of toxin A into animal intestine triggers secretion of fluid and intestinal inflammation characterized by epithelial cell destruction and neutrophil activation. A critical feature of C. difficile enterotoxicity is communication between enterocytes and lamina propria nerves, macrophages, and mast cells mediated via release of neuropeptides and proinflammatory cytokines.

Acute-Phase Proteins↗

[Direct enteral reinfusion of secretions produced in the upper part of the digestive tract].

Two techniques are presented by which secretions from the upper intestinal tract are reinfused directly, into a more distal part of the intestine. The advantages of the methods described includes: no severe bacterial contamination; the enteral nutrition going on; the possibility to break off progressively; less needs of biochemical correction or compensation; no needs to take into account the production-rate or the release of gas.

Cholestasis↗

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