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1.
M S Ardawi Y S Jamal A A Ashy H Nasr E A Newsholme 《The Journal of laboratory and clinical medicine》1990,115(6):660-668
The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues. 相似文献
2.
Effect of glucocorticoid treatment on glucose and glutamine metabolism by the small intestine of the rat 总被引:1,自引:0,他引:1
M Salleh M Ardawi M F Majzoub E A Newsholme 《Clinical science (London, England : 1979)》1988,75(1):93-100
1. The effect of dexamethasone (30 micrograms day-1 100 g-1 body wt.) on the metabolism of glucose and glutamine was studied in the small intestine of rats after 9 days of treatment. 2. Dexamethasone treatment resulted in negative nitrogen balance (P less than 0.001), and produced increases in the concentrations of plasma glucose (22%, P less than 0.05), alanine (32%, P less than 0.001) and insulin (127%, P less than 0.001), but a decrease in the plasma concentration of glutamine (20%, P less than 0.05). 3. Portal-drained visceral blood flow increased by approximately 22% (P less than 0.001) in dexamethasone-treated rats, and was accompanied by a decrease in the arterio-venous concentration difference of glucose (43%, P less than 0.001) and an increase in that of lactate (22%, P less than 0.05), glutamine (35%, P less than 0.01), glutamate (33%, P less than 0.01) and alanine (21%, P less than 0.05). 4. Enterocytes isolated from dexamethasone-treated rats showed decreased and increased rates of glucose and glutamine utilization, respectively. 5. The maximal activities of hexokinase, 6-phosphofructokinase, citrate synthase and oxoglutarate dehydrogenase were decreased (30-64%, P less than 0.001) in intestinal mucosal scrapings of dexamethasone-treated rats, whereas the activity of glutaminase was increased (35%, P less than 0.001). 6. It is concluded that glucocorticoid administration decreases the rate of glucose utilization but increases that of glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells. 相似文献
3.
M. Plauth A. Raible D. Bauder-Groß D. Vieillard-Baron P. Fürst F. Hartmann 《Zeitschrift für die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie》1991,191(1):349-357
Post-stress metabolism is associated with a large glutamine (Gln) efflux from muscle and an increased Gln utilization by the
small intestine. Both appear to be modulated by corticosteroids. The present investigation was performed to better characterize
the mechanism of corticoid action on Gln metabolism in an isolated preparation of vascularly perfused rat small intestine.
In all perfusions, a synthetic perfusate free from blood components was used with only 0.6 mM Gln and 10 mM glucose as substrates. Irrespective of dexamethasone concentrations in the vascular perfusate (none, 0.25 mg l−1, or 2.5 mg l−1), isolated intestines from normal rats exhibited unchanged extraction rates of Gln (−85±8, −89±10, and −87±16 nmol min−1 g−1) and unchanged production rates of alanine (43±9, 40±7, and 51±5 nmol min−1 g−1) and ammonia (49±15, 45±13, and 54±13 nmol min−1 g−1).
Similarly, when intestines were vascularly perfused 2 or 9 days after dexamethasone injection (0.45 mg kg−1 BW), net Gln uptake also remained unchanged (−88±16 and −84±11 nmol min−1 g−1). There was, however, a shift in nitrogenous products of Gln metabolism from ammonia (−31% and −38%) to alanine (+16% and
+64%). Thus, the failure of dexamethasone to increase Gln uptake in the isolated rat intestine may indicate that rather than
acting directly on the mucosa, dexamethasone could regulate intestinal Gln consumption in vivo by indirect mechanisms possibly
involving extramucosal tissues. Dexamethasone pretreatment may modulate the pattern of nitrogenous products in portal venous
blood presented to the liver and thus support enhanced nitrogen loss through ureagenesis by metabolic cooperation between
gut and liver. 相似文献
4.
F L Weber J G Banwell K M Fresard J H Cummings 《The Journal of laboratory and clinical medicine》1987,110(3):259-263
To determine how lactulose and lactulose plus neomycin might alter nitrogen metabolism in the colon we investigated the effect of these agents on the distribution of nitrogen in the bacterial, soluble, and fiber fractions of stool. The alterations in fecal nitrogen excretion were additionally correlated with changes in total body urea synthesis and degradation rates. Six patients with stable cirrhosis received a control diet alone followed by the administration of lactulose (56 +/- 6 gm/day), and eight similar patients received lactulose alone (63 +/- 5 gm/day) followed by the addition of neomycin (4 gm/day). Their feces were partitioned into individual fractions by physical separation. Lactulose administration increased nitrogen excreted in the bacterial fraction by 165% (from 0.52 +/- 0.14 gm/day to 1.38 +/- 0.21 gm/day) and by 135% in the soluble fraction (from 0.58 +/- 0.08 gm/day to 1.36 +/- 0.23 gm/day). When lactulose was supplemented with neomycin, the nitrogen content of the bacterial fraction decreased by 28%. Lactulose caused a 23% reduction in the urea production rate that was mainly accounted for by increase in fecal nitrogen excretion. The addition of neomycin caused a further reduction in urea production that was explained by an inhibition of urea degradation. These results demonstrate that a major effect of lactulose was to augment the incorporation of nitrogen into fecal bacteria although nitrogen in the soluble fraction also increased. The additional nitrogen excreted in the fecal bacterial and soluble fractions caused a reduction in urea synthesis. 相似文献
5.
U Brenner L Herbertz M Meibert J M Müller H Reinauer 《Infusionstherapie und klinische Ern?hrung》1987,14(6):248-251
20 male adult Sprague-Dawley rats were fed exclusively parenterally. After achieving metabolic equilibrium they received a duodenoileostomy and subtotal resection leaving only 8-10% of the small gut. On the 1st postoperative day the urinary 3-MH excretion rose to 1.5-1.7 times the preoperative level, but on the 12th-14th postoperative day it fell again and was equal to the preoperative basal level. A control group of 10 rats undergoing a small gut anastomosis without resection yielded similar results. We conclude that the small gut source does not make a significant contribution to 24h-urinary 3-MH excretion in the adult rat. The transient postoperative increase in urinary 3-MH excretion is probably due to post-injury metabolism. In contrast to these are the measurements in two male patients with a short bowel syndrome because of an occlusion of the superior mesenteric artery. Both patients have a body weight of 60 kg, are aged 44 and 45 years respectively, and have a 24h-urinary 3-MH excretion of 120.7 +/- 28 mumol. More than 1 year after operation they are being nourished parenterally in metabolic equilibrium. The 24h-urinary 3-MH excretion in a similar control group of 8 healthy male volunteers is 229.4 +/- 25 mumol (measurements for 6 days after a 1-week meat-free diet). We conclude that the small gut source makes a significant contribution to 24h-urinary 3-MH excretion in the adult human. There is no evident correlation between the rat model and measurements in human. 相似文献
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1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and glucose was studied in rats made septic by caecal ligation and puncture and was compared with that in rats that had undergone sham operation (laparotomy). 2. Sepsis resulted in increases in the plasma activities of gamma-glutamyltransferase (P less than 0.001), alanine aminotransferase (P less than 0.001) and aspartate aminotransferase (P less than 0.001), the serum total and direct bilirubin concentrations (P less than 0.001), and the blood lactate (P less than 0.01), glutamine (P less than 0.05), alanine (P less than 0.001) and urea (P less than 0.05) concentrations, but produced decreases in the blood ketone body (P less than 0.001) and glutathione (P less than 0.05) concentrations and in the plasma cholesterol concentration (P less than 0.05). These changes were associated with marked negative nitrogen balance in septic rats. 3. Sepsis increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%) and ammonia (by 259%) with concomitant increases in the net rates of hepatic release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and urea (by 100.4%). 4. Sepsis increased the activities of liver carbamoylphosphate synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate synthase (by 28.1%) and arginase (by 33.8%). 5. Septic rats exhibited marked increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%) contents. These changes were accompanied by marked increases in the activity of thymidine kinase (by 35.9%).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonaemia in chronic liver disease 总被引:3,自引:0,他引:3
Ammonia and glutamine metabolism was studied in slices from normal, fatty and cirrhotic human livers. The liver disease was evaluated by histological examination. With respect to ammonia removal, urea and glutamine synthesis in human liver represent low and high affinity systems with k0.5(NH4+) values of 3.6 and 0.11 mM, respectively. Compared with normal control livers, cirrhotic livers showed a decreased glutamine synthesis from NH4Cl by about 80%. The same was true for urea synthesis. Conversely, flux through hepatic glutaminase was increased in cirrhosis 4-6-fold. These changes in hepatic glutamine and ammonia metabolism were observed regardless of whether reference was made to liver wet weight, DNA or protein content. Acetazolamide inhibited urea synthesis in cirrhotic liver slices by about 50%, indicating that mitochondrial carbonic anhydrase is required for urea synthesis also in cirrhosis. There was a significant correlation between the in-vitro determined capacity for urea synthesis from NH4Cl and the in-vivo determined plasma bicarbonate concentration.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
H G Preuss D Byrne P S Shim 《The Journal of pharmacology and experimental therapeutics》1976,197(1):199-205
After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity. 相似文献
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11.
乳果糖对肠道菌群及SIgA含量的影响 总被引:8,自引:0,他引:8
目的 分析31名血液病患儿服用乳果糖前后肠道菌群及SIgA含量。方法 用培养方法检测肠道菌群,用单向琼脂免疫扩散法测定粪便中SIgA。结果 服用乳果糖后,血液病患儿肠道内双歧杆菌数量增加,分泌SIgA水平上升。结论 乳果糖刺激机体肠道内双杆菌生长以及免疫系统分泌SIgA,增加肠道局部免疫力。 相似文献
12.
K Koyama Y Owada H Yamauchi K Ito S Watabe T Sato 《The Tohoku journal of experimental medicine》1979,127(4):379-387
Arginine synthetase activity and ammonia removal in liver slices were determined in rats with obstructive jaundice or acute carbon tetrachloride (CCl4)-induced liver dysfunction and the following results were obtained: (1) Urea synthesis and ammonia removal in liver slices progressively decreased with prolonged biliary obstruction. The effects of ATP and/or ornithine addition were also markedly decreased, particularly in the group with 6 weeks of biliary obstruction. (2) Arginine synthetase activity also fell with prolongation of biliary obstruction and the fall was most pronounced in the 6-week group. (3) The CCl4-induced liver dysfunction group showed a significantly higher level of arginine synthetase activity than the group with 6 weeks of biliary obstruction, but ammonia removal was markedly decreased and the effects of ATP and ornithine addition were prominent. From the results, it is concluded that, due to a fall in the enzyme activity of the urea cycle in obstructive jaundice, liver dysfunction can easily occur with prolongation of the obstruction, while hepatic urea cycle dysfunction is brought about by severe metabolic disruption in the liver damaged by CCl4. 相似文献
13.
Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). 总被引:8,自引:1,他引:8
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C Florent B Flourie A Leblond M Rautureau J J Bernier J C Rambaud 《The Journal of clinical investigation》1985,75(2):608-613
The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and beta-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents. Moreover, 14C-lactulose was added to cold lactulose and 14CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P less than 0.05), whereas 14CO2 excretion increased (P less than 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas beta-galactosidase activity rose markedly (P less than 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P less than 0.01), while an increase was found for lactic acid (P less than 0.001), acetic acid (P less than 0.0001), and total VFA (P less than 0.001). Cecal fluid pH dropped faster (P less than 0.05) and to a lower level (P less than 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate. 相似文献
14.
Effects of neomycin and penicillin administration on mucosal proliferation of the mouse small intestine. With morphological and functional correlations 总被引:3,自引:1,他引:2
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The effects of an oral neomycin and penicillin regimen on intestinal bacteriology and on morphology and function of the small intestine of mice were investigated. Quantitative and qualitative stool cultures on selective media of the treated animals revealed only growth of yeast organisms. The treated animals developed enlargement of the ceca with fluid contents and watery stools, resembling characteristics of germfree animals. Radioautography with tritiated thymidine revealed an increased epithelial cell migration rate in the mice treated with the antibiotics for 3 to 5 wk. A slight increase in villus height was also noted. The treated male mice showed greater variance than the treated females in epithelial cell migration rates. Histochemical staining reactions showed a decrease in nonspecific esterase and in NADH dehydrogenase activity in the proximal gut of the antibiotic animals. Stains of distal gut and those for acid and alkaline phosphatase, NADPH dehydrogenase, lactic dehydrogenase, and succinic dehydrogenase were similar to the controls. A slight increase in sucrase activity and a slight decrease in lactase activity in the antibiotic animals was observed in contrast to control animals. Germfree mice, however, had greater sucrase and lactase activity. Transport of L-methionine was slightly reduced in the distal segment of the treated animals. Since the direction of these changes is away from the intestinal state observed in germfree animals, they are probably the result of the direct action of the antibiotics on the gut. 相似文献
15.
Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat. 总被引:1,自引:0,他引:1
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Renal glutamine uptake and subsequent urinary ammonia excretion could be an important alternative pathway of ammonia disposal from the body during liver failure (diminished urea synthesis), but this pathway has received little attention. Therefore, we investigated renal glutamine and ammonia metabolism in midly hyperammonemic, portacaval shunted rats and severely hyperammonemic rats with acute liver ischemia compared to their respective controls, to investigate whether renal ammonia disposal from the body is enhanced during hyperammonemia and to explore the limits of the pathway. Renal fluxes, urinary excretion, and renal tissue concentrations of amino acids and ammonia were measured 24 h after portacaval shunting, and 2, 4, and 6 h after liver ischemia induction and in the appropriate controls. Arterial ammonia increased to 247 +/- 22 microM after portacaval shunting compared to controls (51 +/- 8 microM) (P < 0.001) and increased to 934 +/- 54 microM during liver ischemia (P < 0.001). Arterial glutamine increased to 697 +/- 93 microM after portacaval shunting compared to controls (513 +/- 40 microM) (P < 0.01) and further increased to 3781 +/- 248 microM during liver ischemia (P < 0.001). In contrast to controls, in portacaval shunted rats the kidney net disposed ammonia from the body by diminishing renal venous ammonia release (from 267 +/- 33 to -49 +/- 59 nmol/100 g body wt per min) and enhancing urinary ammonia excretion from 113 +/- 24 to 305 +/- 52 nmol/100 g body wt per min (both P < 0.01). Renal glutamine uptake diminished in portacaval shunted rats compared to controls (-107 +/- 33 vs. -322 +/- 41 nmol/100 g body wt per min) (P < 0.01). However, during liver ischemia, net renal ammonia disposal from the body did not further increase (294 +/- 88 vs. 144 +/- 101 nmol/100 g body wt per min during portacaval shunting versus liver ischemia). Renal glutamine uptake was comparable in both hyperammonemic models. These results indicate that the rat kidney plays an important role in ammonia disposal during mild hyperammonemia. However, during severe liver insufficiency induced-hyperammonemia, ammonia disposal capacity appears to be exceeded. 相似文献
16.
1. The metabolism of glucose and glutamine was studied in the small intestine and the colon of rats after 4-5 weeks of hypothyroidism. 2. Hypothyroidism resulted in increases in the plasma concentrations of ketone bodies (P less than 0.05), cholesterol (P less than 0.001) and urea (P less than 0.001), but decreases in the plasma concentrations of free fatty acids (P less than 0.05) and triacylglycerol (P less than 0.001). These changes were associated with decreases in the plasma concentrations of total tri-iodothyronine, free tri-iodothyronine, total thyroxine and free thyroxine. 3. Hypothyroidism decreased both the DNA content (by 30.5%) and the protein content (by 23.6%) of intestinal mucosa, with the protein/DNA ratio remaining unchanged. The villi in the jejunum were shorter (P less than 0.05) and the crypt depth was decreased by about 26.5% in hypothyroid rats. 4. Portal-drained visceral blood flow showed no marked change in response to hypothyroidism, but was accompanied by decreased rates of extraction of glucose, lactate and glutamine and release of glutamate, alanine and ammonia. 5. Enterocytes and colonocytes isolated from hypothyroid rats showed decreased rates of utilization and metabolism of glucose and glutamine. 6. The maximal activities of hexokinase (EC 2.7.1.1), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), citrate synthase (EC 4.1.3.28), oxoglutarate dehydrogenase (EC 1.2.4.2) and phosphate-dependent glutaminase (EC 3.5.1.2) were decreased in intestinal mucosal scrapings from hypothyroid rats. Similar decreases were obtained in colonic mucosal scrapings (except for citrate synthase and oxoglutarate dehydrogenase) from hypothyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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H J Binder L A Katz R P Spencer H M Spiro 《The Journal of clinical investigation》1966,45(12):1854-1858
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