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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Inter-organ relationships between glucose, lactate and amino acids were studied by determination of plasma concentrations in different blood vessels of anaesthetized rats fed on either a high-carbohydrate diet [13% (w/w) casein, 79% (w/w) starch] or a high-protein diet [50% (w/w) casein, 42% (w/w) starch]. The period of food intake was limited (09:00-17:00h), and blood was collected 4h after the start of this period (13:00h). 2. Glucose absorption was considerable only in rats fed on a high-carbohydrate diet. Portal-vein-artery differences in plasma lactate concentration were higher in rats fed on this diet, but not proportional to glucose absorption. Aspartate, glutamate and glutamine were apparently converted into alanine, but when dietary protein intake was high, a net absorption of glutamine occurred. 3. The liver removed glucose from the blood in rats fed on a high-carbohydrate diet, but glucose was released into the blood in rats fed on the high-protein diet, probably as a result of gluconeogenesis. Lactate uptake was very low when amino acid availability was high. 4. In rats on a high-protein diet, increased uptake of amino acids, except for ornithine, was associated with a rise in portal-vein plasma concentrations, and in many cases with a decrease in hepatic concentrations. 5. Hepatic concentrations of pyruvate and 2-oxo-glutarate decreased without a concomitant change in the concentrations of lactate and malate in rats fed on the high-protein diet, in spite of an increased supply of pyruvate precursors (e.g. alanine, serine, glycine), suggesting increased pyruvate transport into mitochondria. 6. High postprandial concentrations of plasma glucose and lactate resulted in high uptakes of these metabolites in peripheral tissues of rats on both diets. Glutamine was released peripherally in both cases, whereas alanine was taken up in rats fed on a high-carbohydrate diet, but released when the amino acid supply increased. 7. It is concluded that: the small intestine is the main site of lactate production, and the peripheral tissues are the main site for lactate utilization; during increased ureogenesis in fed rats, lactate is poorly utilized by the liver; the gut is the main site of alanine production in rats fed on a high-carbohydrate diet and the liver utilizes most of the alanine introduced into the portal-vein plasma in both cases.
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PMID:Inter-organ relationships between glucose, lactate and amino acids in rats fed on high-carbohydrate or high-protein diets. 63 46

IN AN EFFORT TO DOCUMENT THE ROLE OF THE LIVER IN THE CATABOLISM OF VASOACTIVE INTESTINAL PEPTIDE, SEVERAL DIFFERENT TYPES OF EXPERIMENTS WERE CARRIED OUT, INCLUDING: 1) simultaneous measurement of portal and systemic immunoreactive vasoactive intestinal peptide, both in the basal state and following calcium stimulation; 2) by measuring plasma concentrations of immunoreactive vasoactive intestinal peptide before and after portacaval shunt; 3) by measuring plasma VIP before and after portacaval shunt following calcium, prostigmine and pentagastrin stimulation; 4) by determining plasma VIP levels in patients with liver disease and in hepatic failure, and in patients with variceal hemorrhage before and serially after portal systemic shunt; 5) by measuring CSF vasoactive intestinal peptide in dogs before and after portacaval shunt and when the animals finally succumb to hepatic failure. The results consistently suggest that the shunting of portal blood away from the liver does not result in significant elevation of basal peripheral plasma levels of vasoactive intestinal peptide. Following stimulation however, increased amounts of peripheral plasma VIP are detected, following calcium, pentagastrin and prostigmine release of VIP. Portal vein levels are always significantly higher than peripheral plasma VIP again, confirming a catabolic role for the liver. In patients, elevation of peripheral plasma VIP is seen in hepatic failure, but not after portacaval shunt. Finally, cerebrospinal fluid VIP is elevated in dogs following hepatic failure, confirming the presence of a neural-gut axis and suggesting an influence of hepatic catabolism of VIP not only in the periphery, but also within the central nervous system.
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PMID:Hepatic inactivation of vasoactive intestinal peptide in man and dog. 66 73

1. The extent of propionate metabolism during absorption from the gut and the amounts of L-lactate formed and glucose utilized by the portal-drained viscera were determined in conscious sheep from measurements of portal venous blood flow and portal venous and aortic metabolite concentrations. The sheep were fasted overnight and given primed continuous intraruminal infusions of volatile fatty acids (VFA) at two rates, supplying propionate at 40.0 and 79.9 mmol/h. Measurements were made during the 5th and 6th hours of the infusion, when rumen liquor VFA concentrations were constant. 2. The rate of L-lactate formation by the portal-drained viscera was not affected by the VFA infusions and accounted for approximately 15% of the probably total lactate entry rate. 3. Considerable amounts of glucose were taken up by the portal-drained viscera, amounting to approximately 35% of the probable glucose entry rate. If this glucose was metabolized through the glycolytic pathway, this would at all times have accounted for the amounts of L-lactate formed. 4. Portal venous blood flow was positively correlated with VFA infusion rates and with the net amount of propionate appearing in the portal blood. 5. It is concluded that although propionate may be metabolized by the rumen epithelium, the unique pathway of L-lactate formation from propionate is of limited quantitative significance to the animal, although it may be of importance to the rumen epithelium itself.
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PMID:Metabolism of propionate in the tissues of the sheep gut. 112 72

1. Measurements were made of portal blood flow, heat production and oxygen consumption in the digestive tract of sheep either fasted or given the following diets: chopped, dried grass, pelleted, dried grass; chopped, dried lucerne; pelleted, dried lucerne, or a pelleted barley diet. 2. For sheep that had been fasted for 48 h, portal blood flow was 1.84 l/min, total visceral heat production was 62.3 kJ/kg body-weight 0.75 per 24 h and aerobic heat production, estimated from oxygen consumption, was 62.1 kJ/kg body-weight 0.75 per 24 h. 3. Portal blood flow was markedly influenced by food intake, increasing from 1.8 l/min for starved sheep to 2.4 and 4 l/min for sheep feed at maintenance and 2.5 times maintenance levels of intake respectively. Variations in the quality and physical form of the diets had no apparent effect on portal blood flow. 4. There was a curvilinear relationship between total heat production in the gut and metabolizable energy (ME) intake. The increase obtained for levels of intake below maintenance was greatest with lucerne diets, and least with pelleted, dried grass or pelleted barley diets. Above maintenance levels of intake the rate of increase in heat production, with all diets, was about 150 kJ/MJ ME intake. 5. The heat of fermentation, estimated from the difference between total visceral metabolism and the aerobic metabolism of the tissues of the gut wall, was 76, 60 and 22 kJ/MJ digestible energy intake for the dried grass, lucerne and barley diets respectively. 6. The contribution of fermentation heat and the aerobic metabolism of the gut to the total heat increment of feeding in sheep was assessed. It was concluded that about half the heat increment must be derived from tissues outside the digestive tract.
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PMID:The influence of food intake on portal blood flow and heat production in the digestive tract of sheep. 114 50

1. After operation, changes in nitrogen metabolism occur. Although increased flux of amino acids from peripheral to splanchnic organs after operation has been described, substrate utilization by the individual organs in the splanchnic area is less well characterized. We were specifically interested in substrate flux across the spleen as it is an organ with important immunological functions. 2. Therefore, hindquarter, gut, spleen and liver fluxes of amino acids, ammonia, glucose, lactate and blood gases were measured for 4 days after a standard operation in pigs. In a separate control group, fluxes were measured 2-3 weeks after this operation and these values were assumed to represent the normal situation. 3. One day after operation, the hindquarter effluxes of glutamine, alanine and several essential amino acids were increased (P > 0.001), but these normalized at the end of the observation period. In the same period, liver glutamine uptake increased (P < 0.01), concomitantly with increased HCO3-, glucose and urea production, which also normalized. Portal drained viscera ammonia production decreased, concomitant with decreased glutamine uptake (P < 0.001). After operation, the splenic release of ammonia increased sevenfold (P < 0.05) and that of lactate increased from -158 +/- 544 to 3294 +/- 642 nmol min-1 kg-1 body weight (P < 0.001). Glucose uptake increased from -964 +/- 632 to -3933 +/- 1524 nmol min-1 kg-1 body weight and glutamine efflux (391 +/- 143) reversed to uptake (-752 +/- 169 nmol min-1 kg-1 body weight) (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. 133 99

Portal circulation was reduced to 50-60% for one hour by partial occlusion of the superior mesenteric artery for the purpose of studying the relationship between reperfusion injury, bacterial translocation and multiple system organ failure. Forty dogs were divided randomly into four groups, and 1 x 10(10)/kg E. coli O111B4 were fed to each animal 12 hours before operation. Group I constituted the controls, in which sham operations were performed. The experimental procedure was completed in all the animals of the other three groups. Rubia yunnanensis, an anti-oxidant, was given to group III. Amikacin was given to group IV. The results showed that group II was characterized by bacteremia, hypoxemia, and hypotension as compared with group I. The levels of superoxide dismutase (SOD) in the whole blood were markedly lowered and malondialdehyde (MDA) values significantly elevated in group II after reperfusion compared with group I. Plasma levels of anaphylatoxin C5a and B2 (TXB2) were significantly raised in group II beginning with the reperfusion when compared with groups I, III and IV. Pathological changes in the intestine, liver and lung were remarkable only in group II, including acute necrosis of the intestinal mucosa, granulocyte infiltration, hemorrhage and edema of the lung, degenerative changes of myocardial and hepatic cells, and bacterial invasion of the blood, liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development to multiple system organ failure (MSOF) by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations where it fuels the septic process. Oxygen free radicals, anaphylatoxin and thromboxane may be potential factors in the development of gut barrier failure and MSOF.
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PMID:Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion. 180 29

Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury.
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PMID:The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury. 190 74

Recent animal data suggest that the gut plays a far more important metabolic role than previously thought. During critical illness, disruption in bowel barrier function may result in a chronic hypermetabolic state and contribute to multiorgan failure. Animal studies have demonstrated that enterocytes of the gastrointestinal tract use glutamine as a respiratory fuel and during critical illness the consumption of glutamine by the gut significantly increases. The selective uptake of glutamine by the gut, to date, has not been confirmed in humans. Seven patients who sustained multisystem trauma necessitating laparotomy underwent portal venous catheterization. This was done by carefully reopening the obliterated umbilical vein and facilitating access to the left branch of the portal vein using a standard central venous catheter. Portal venous and systemic blood samples were recorded for 5 days after operation. Amino acid levels in both circulations were recorded at 48 h and 5 days. Using Student's t test for related samples, the differences between individual amino acids in portal and systemic circulations were compared. At 48 h, mean(s.d.) portal venous glutamine was 85(5) per cent of the systemic levels (253(80) compared with 296(90) mumol/ml, P less than 0.002). At 5 days, portal glutamine was 87(3) per cent of the systemic levels (255(69) compared with 292(83) mumol/ml, P less than 0.003). Levels of citrulline, a breakdown product of glutamine metabolism, were elevated in the portal venous circulation at 48 h (20(4) compared with 16(3) mumol/ml, P less than 0.005) and at 5 days (21(5) compared with 14(3) mumol/ml, P less than 0.002). No significant differences between any of the other amino acids analysed were identified. This study confirms, for the first time in humans, that selective uptake of glutamine occurs in the gut. In stressed states, glutamine deficiency is associated with gut mucosal atrophy. This has significant implications as glutamine is not provided in most commercially available parenteral and enteral nutrition formulations.
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PMID:Selective uptake of glutamine in the gastrointestinal tract: confirmation in a human study. 155 3

Ammonia is generated from a large number of metabolically important reactions. Despite its central importance in whole body nitrogen homeostasis excess ammonia is neurotoxic and its concentration must be kept low. Ammonia generated in most extrahepatic tissues is detoxified by incorporation into glutamine (amide). This glutamine may be used in a number of biosynthetic reactions (e.g. in pyrimidine synthesis). Alternatively, as a means of maintaining nitrogen balance, glutamine may be released to the blood. Resting skeletal muscle is particularly important 1) as a "sink" for removal of blood ammonia, and 2) as a major source of circulating glutamine. However, during vigorous exercise skeletal muscle may become a net contributor of ammonia to the blood. A few tissues and cell types (e.g. lymphocytes, macrophages, enterocytes, colonocytes, thymocytes, fibroblasts, bone) and tumors exhibit marked rates of glutamine utilization. In the kidney, glutamine is an important source of urinary ammonia. Ammonia generated from 1) the breakdown of nitrogenous substances in the gut, and 2) from the use of glutamine as a metabolic fuel in the small intestine, is taken up by the liver wherein it is detoxified by conversion to urea and to a lesser extent, glutamine. Some portal vein glutamine acts as a source of urea nitrogen. Ultimately, however, most excess ammonia nitrogen is detoxified indirectly (via glutamine (blood)----glutamine (small intestine)----ammonia (portal vein) or directly in the liver as urea. Portal-systemic shunting of blood, as occurs in chronic cirrhosis of the liver or following the surgical construction of a portacaval shunt results in portal blood bypassing the normal ammonia detoxification machinery of the liver. Under this condition blood ammonia levels rise markedly, increasing the burden on extrahepatic tissues, such as skeletal muscle, brain, and kidney, in maintaining ammonia homeostasis. The most commonly employed animal model of human liver disease is the rat in which an end-to-side portacaval shunt (PCS) has been surgically constructed. Brain glutamine synthetase activity is not increased in PCS rats and in some areas of the brain there may even be a decrease in activity. The brain glutamine synthetase appears to be working at near maximal capacity. Thus, the PCS rats exhibit profound neurological dysfunction when administered ammonium salts in amounts easily tolerated by normal animals. Because of the limited capacity of brain to remove excess ammonia, a rational approach to the treatment of patients with liver disease should include a regimen directed toward lowering the associated hyperammonemia.
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PMID:Ammonia metabolism in normal and portacaval-shunted rats. 210 90

Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on the roles of endotoxin and tumor necrosis factor alpha (TNF alpha). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 +/- 0.50 U/mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 +/- 3.11 U/mL, p greater than 0.05 and 10.41 +/- 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury.
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PMID:Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. 217 68


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