Effect of glucocorticoid treatment on glucose and glutamine metabolism by the small intestine of the rat

1988 ◽  
Vol 75 (1) ◽  
pp. 93-100 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
May F. Majzoub ◽  
Eric A. Newsholme
Keyword(s):  
Small Intestine ◽  
Glucose Utilization ◽  
Citrate Synthase ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Glucocorticoid Treatment ◽  
Concentration Difference ◽  
Oxoglutarate Dehydrogenase

1. The effect of dexamethasone (30 μg 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 < 0.001), and produced increases in the concentrations of plasma glucose (22%, P < 0.05), alanine (32%, P < 0.001) and insulin (127%, P < 0.001), but a decrease in the plasma concentration of glutamine (20%, P < 0.05). 3. Portal-drained visceral blood flow increased by approximately 22% (P < 0.001) in dexamethasone-treated rats, and was accompanied by a decrease in the arteriovenous concentration difference of glucose (43%, P < 0.001) and an increase in that of lactate (22%, P < 0.05), glutamine (35%, P < 0.01), glutamate (33%, P < 0.01) and alanine (21%, P < 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 < 0.001) in intestinal mucosal scrapings of dexamethasone-treated rats, whereas the activity of glutaminase was increased (35%, P < 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.

Effects of hypothyroidism on glucose and glutamine metabolism by the gut of the rat

1991 ◽  
Vol 81 (3) ◽  
pp. 347-355 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Sawsan M. Jalalah
Keyword(s):  
Small Intestine ◽  
Citrate Synthase ◽  
Ketone Bodies ◽  
Plasma Concentrations ◽  
Marked Change ◽  
Glutamine Metabolism ◽  
Total Thyroxine ◽  
Oxoglutarate Dehydrogenase

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 < 0.05), cholesterol (P < 0.001) and urea (P < 0.001), but decreases in the plasma concentrations of free fatty acids (P < 0.05) and triacylglycerol (P < 0.001). These changes were associated with decreases in the plasma concentrations of total triiodothyronine, 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 < 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. 7. It is concluded that hypothyroidism decreases the rates of utilization of glucose and glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine and colon. This may be caused by changes in protein turnover and/or the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells.

Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats

1990 ◽  
Vol 79 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Yasir S. Jamal
Keyword(s):  
Skeletal Muscle ◽  
Exchange Rates ◽  
Skeletal Muscles ◽  
Plasma Concentrations ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls. 5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased. 6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.

Glutamine metabolism in the lungs of glucocorticoid-treated rats

1991 ◽  
Vol 81 (1) ◽  
pp. 37-42 ◽  
Author(s):  
M. Salleh ◽  
M. Ardawi
Keyword(s):  
Exchange Rates ◽  
Marked Change ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference ◽  
Blood Concentrations ◽  
Glucocorticoid Administration

1. The effect of dexamethasone (30 μg day−1 100 g−1 body weight) on the regulation of glutamine metabolism was studied in the lungs of rats after 9 days of treatment. 2. Dexamethasone resulted in a negative nitrogen balance, and produced decreases in the blood concentrations of glutamine (32.3%) and glutamate (25.3%) but an increase in the blood concentration of alanine (33.9%). 3. Dexamethasone treatment increases the rates of production of glutamine and alanine by lung slices incubated in vitro. 4. Blood flow and arteriovenous concentration difference measurement across the lungs exhibited an increase in the net exchange rates of glutamine (131.6%) and alanine (113.2%) in dexamethasone-treated rats compared with corresponding pair-fed controls. 5. Dexamethasone treatment produced significant decreases in the lung concentrations of glutamine (47.2%), glutamate (30.9%) and 2-oxoglutarate (57.3%). The concentrations of alanine (52.1%), ammonia (24.7%) and pyruvate (43.7%) were increased. 6. The maximal activity of glutamine synthetase was increased (21.5%), but there was no marked change in that of glutaminase, in the lungs of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of production of glutamine and alanine from lungs of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular biosynthesis of glutamine and alanine.

scholarly journals Glutamine gluconeogenesis in the small intestine of 72 h-fasted adult rats is undetectable

2006 ◽  
Vol 401 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Guy Martin ◽  
Bernard Ferrier ◽  
Agnès Conjard ◽  
Mireille Martin ◽  
Rémi Nazaret ◽  
...  
Keyword(s):  
Small Intestine ◽  
Glucose Production ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Concentration Difference ◽  
Adult Rat ◽  
Nutrition And Diabetes ◽  
Glucose Synthesis

Recent reports have indicated that 48–72 h of fasting, Type 1 diabetes and high-protein feeding induce gluconeogenesis in the small intestine of adult rats in vivo. Since this would (i) represent a dramatic revision of the prevailing view that only the liver and the kidneys are gluconeogenic and (ii) have major consequences in the metabolism, nutrition and diabetes fields, we have thoroughly re-examined this question in the situation reported to induce the highest rate of gluconeogenesis. For this, metabolically viable small intestinal segments from 72 h-fasted adult rats were incubated with [3-13C]glutamine as substrate. After incubation, substrate utilization and product accumulation were measured by enzymatic and NMR spectroscopic methods. Although the segments utilized [13C]glutamine at high rates and accumulated 13C-labelled products linearly for 30 min in vitro, no substantial glucose synthesis could be detected. This was not due to the re-utilization of [13C]glucose initially synthesized from [13C]glutamine. Arteriovenous metabolite concentration difference measurements across the portal vein-drained viscera of 72 h-fasted Wistar and Sprague–Dawley rats clearly indicated that glutamine, the main if not the only gluconeogenic precursor taken up, could not give rise to detectable glucose production in vivo. Therefore we challenge the view that the small intestine of the adult rat is a gluconeogenic organ.

scholarly journals Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition

Blood ◽  
2018 ◽  
Vol 131 (15) ◽  
pp. 1639-1653 ◽  
Author(s):  
Paolo Gallipoli ◽  
George Giotopoulos ◽  
Konstantinos Tzelepis ◽  
Ana S. H. Costa ◽  
Shabana Vohra ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Glucose Utilization ◽  
Glutamine Metabolism ◽  
Key Points ◽  
Mutant Cells ◽  
Acute Myeloid

Key PointsFLT3ITD TK inhibition impairs glycolysis and glucose utilization without equally affecting glutamine metabolism. Combined targeting of FLT3 TK activity and glutamine metabolism decreases FLT3ITD mutant cells leukemogenic potential in vitro and in vivo.

scholarly journals Metabolism and transport of glutamine and glucose in vascularly perfused small intestine of the rat

1977 ◽  
Vol 166 (3) ◽  
pp. 509-519 ◽  
Author(s):  
Peter John Hanson ◽  
Dennis Shirley Parsons
Keyword(s):  
Small Intestine ◽  
Glucose Utilization ◽  
Unit Length ◽  
Lactate Production ◽  
Glutamine Metabolism ◽  
Vascular Bed ◽  
Alanine Production

1. The metabolism and transport of glutamine and glucose were investigated in a preparation of rat small intestine perfused through the vascular bed in vitro and in situ. 2. With glucose (7.5mm) or glutamine (4.5mm) in the lumen, approx. 40% of the substrate taken up appears unchanged on the vascular side. When glutamine (1.5mm) is also added to the vascular perfusate, metabolism of glutamine is increased and there is uptake of glutamine from both the vascular bed and lumen. Orientation of substrate (vascular bed or lumen) influences the value of alanine production/glutamine utilization and lactate production/glucose utilization. 3. Deprivation of food and metabolic acidosis have no effect upon the utilization of glutamine by unit length of jejunum. In fed rats, glutamine utilization is 44% of glucose utilization, but in rats deprived of food it is 112% of glucose utilization. 4. Glucose utilization and lactate production are not significantly altered by the presence of glutamine in the vascular bed or lumen. 5. With glucose only in the vascular perfusate, glucose utilization is the same in jejunum and ileum. Glutamine metabolism in the ileum is 28% lower than in the jejunum. 6. Glutamine utilization is dependent on the concentration of glutamine in the vascular perfusate, but is not significantly affected by the absence of glucose. 7. Results are discussed in relation to the role of intestinal glutamine metabolism and with respect to some problems of the transepithelial movement of substrates that are both transported and metabolized.

scholarly journals Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moe Ichikawa ◽  
Hiroki Akamine ◽  
Michika Murata ◽  
Sumito Ito ◽  
Kazuo Takayama ◽  
...  
Keyword(s):  
Small Intestine ◽  
Drug Absorption ◽  
Cell Model ◽  
Negative Effects ◽  
Piggybac Transposon ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cyp3a4 Expression

AbstractCaco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.

scholarly journals Absorption of lactulose from mammalian gastrointestinal tract

1979 ◽  
Vol 41 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. F. Evered ◽  
F. Sadoogh-Abasian
Keyword(s):  
Small Intestine ◽  
Calcium Ions ◽  
Clinical Evidence ◽  
Buccal Cavity ◽  
Rat Small Intestine ◽  
Sodium Ions ◽  
Mode Of Transport ◽  
Poor Absorption

1. The disaccharide lactulose (galactosyl-β-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo.2. These results confirm indirect clinical evidence of poor absorption from the intestine.3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from the buccal cavity.4. The presence of ouabain, or absence of Na+, did not decrease the absorption of lactulose from small intestine.5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.

Glucose utilization by sheep embryos derived in vivo and in vitro

1991 ◽  
Vol 3 (5) ◽  
pp. 571 ◽  
Author(s):  
JG Thompson ◽  
AC Simpson ◽  
PA Pugh ◽  
RW Wright ◽  
HR Tervit
Keyword(s):  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Cell Stage ◽  
Glycolytic Activity ◽  
Total Utilization ◽  
Oxidation Of Glucose

Embryos were collected from superovulated donors at various intervals from onset of oestrus, ranging from Day 1.5 to Day 6. In addition, blastocysts obtained from the culture of 1-cell embryos collected in vivo or of oocytes matured and fertilized in vitro were used to assess the effects of in vitro manipulation and culture on glucose utilization. Glycolytic activity was determined by the conversion of [5-3H]glucose to 3H2O, and oxidation of glucose was determined by the conversion of [U-14C]glucose to 14CO2. Glucose utilization increases significantly from the 8-cell stage and during compaction and blastulation. Glucose oxidation was at a relatively low level (5-12% of total utilization) compared with glycolysis. No difference was observed between the glycolytic activity of blastocysts derived from in vivo or in vitro sources. However, glucose oxidation was lower (P less than 0.05) in blastocysts derived from the culture of 1-cell embryos or from oocytes matured and fertilized in vitro. Exogenous tricarboxylic acid cycle substrates (i.e. pyruvate and lactate supplied in the medium) affected the level of glucose oxidation.

scholarly journals Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1522
Author(s):  
Bin Zeng ◽  
Hailong Wang ◽  
Junyi Luo ◽  
Meiying Xie ◽  
Zhengjiang Zhao ◽  
...  
Keyword(s):  
Small Intestine ◽  
Extracellular Vesicles ◽  
Immunoglobulin A ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Intestinal Immunity ◽  
In Vivo Experiments ◽  
Porcine Milk

Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.

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