Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats

Yang, Hua; Söderholm, J D; Larsson, Jenny; Permert, Johan; Olaison, Gunnar; Wirén, Mikael

doi:10.1016/s0261-5614(98)80028-9

Cited by 14 publications

(11 citation statements)

References 31 publications

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“…Indeed, ACO2, DLD, and MPST, which are enzymes involved in the TCA cycle leading to Acetyl‐CoA oxidation, were downregulated, as well as NDUFS1 and ETFA, suggesting a reduction of energy production in the colon of female ABA mice. Our results are in accordance with previous data showing lower intestinal ATP content in starved rats or inhibited aerobic glycolysis and mitochondrial‐derived ATP generation in glucose‐starved colonic epithelial cells . The assessment of mitochondria morphology by transmission electron microscopy could be of interest in ABA mice.…”

Section: Discussionsupporting

confidence: 93%

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia‐Induced Malnutrition in Mice

et al. 2018

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Anorexia nervosa is an eating disorder often associated with intestinal disorders. To explore the underlying mechanisms of these disorders, the colonic proteome was evaluated during activity-based anorexia. Female C57Bl/6 mice were randomized into three groups: Control, Limited Food Access (LFA) and Activity-Based Anorexia (ABA). LFA and ABA mice had a progressive limited access to food but only ABA mice had access to an activity wheel. On colonic mucosal protein extracts, a 2D PAGE-based comparative proteomic analysis was then performed and differentially expressed proteins were identified by LC-ESI-MS/MS. Twenty-seven nonredundant proteins that were differentially expressed between Control, LFA, and ABA groups were identified. ABA mice exhibited alteration of several mitochondrial proteins involved in energy metabolism such as dihydrolipoyl dehydrogenase and 3-mercaptopyruvate sulfurtransferase. In addition, a downregulation of mammalian target of rapamycin (mTOR) pathway was observed leading, on the one hand, to the inhibition of protein synthesis, evaluated by puromycin incorporation and mediated by the increased phosphorylation of eukaryotic elongation factor 2, and on the other hand, to the activation of autophagy, assessed by the increase of the marker of autophagy, form LC3-phosphatidylethanolamine conjugate/Cytosolic form of Microtubule-associated protein 1A/1B light chain 3 (LC3II/LC3I) ratio. Colonic mucosal proteome is altered during ABA suggesting a downregulation of energy metabolism. A decrease of protein synthesis and an activation of autophagy were also observed mediated by mTOR pathway.

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Section: Discussionsupporting

confidence: 93%

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia‐Induced Malnutrition in Mice

et al. 2018

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“…Although glutamine is a principal energy source for intestinal enterocytes and is considered essential for gut metabolism, structure, and function, glutamine did not restore the intracellular ATP level in the jejunal mucosal cells of malnourished rats (37). Similar to that report, malnutrition decreased ATP content in the right lung and an oral supply of sodium glutamate did not restore ATP content in the lung.…”

Section: Discussionsupporting

confidence: 75%

Malnutrition impairs alveolar fluid clearance in rat lungs

Sakuma

Zhao²,

Sugita³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inadequate nutrition complicates the clinical course of critically ill patients, and many of these patients develop pulmonary edema. However, little is known about the effect of malnutrition on the mechanisms that resolve alveolar edema. Therefore, we studied the mechanisms responsible for the decrease in alveolar fluid clearance in rats exposed to malnutrition. Rats were allowed access to water, but not to food, for 120 h. Then, the left and right lungs were isolated for the measurement of lung water volume and alveolar fluid clearance, respectively. The rate of alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue dye that was instilled into the distal air spaces with an isosmolar 5% albumin solution over 1 h. Malnutrition decreased alveolar fluid clearance by 38% compared with controls. Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats. Either refeeding for 120 h following nutritional deprivation for 120 h or an oral supply of sodium glutamate during nutritional deprivation for 120 h restored alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all conditions (control, malnutrition, refeeding, and glutamate-treated). These results indicate that malnutrition impairs primarily amiloride-insensitive and dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic agonist therapy.

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“…The equipment is commercially available but custom made equipment is also used. The amount of tissue necessary for one set-up ranges from 3.8 mm 2 [125] -5 mm 2 [126] in the smaller version, to 0.65-1.78 cm 2 in the larger version [104,123,[127][128][129]. The smallest chambers (mm 2 -range) have, up to now, only been used for absorption studies [125,126] and are very promising in the light of the scarce availability of human tissue.…”

Section: Ussing Chambermentioning

confidence: 99%

“…The bidirectional supply of glutamine to the incubation medium has been shown beneficial for the viability of Ussing chamber preparations, as it helps to maintain rat enterocyte ATP content in this system [128].…”

Section: Ussing Chambermentioning

confidence: 99%

In Vitro Methods to Study Intestinal Drug Metabolism

Kerkhof¹,

Graaf²,

Groothuis

2007

CDM

108

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Although the liver has long been thought to play the major role in drug metabolism, also the metabolic capacity of the intestine is more and more recognized. In vivo studies eventually pointed out not only the significance of first-pass metabolism by the intestinal wall for the bioavailability of several compounds, but also the relevance of transporters in this process. Only a few methods are available to study drug metabolism in vivo or in situ and with most of these methods it remains difficult to discriminate between the contribution of liver and extrahepatic tissues. To study intestinal drug metabolism in vitro, apart from subcellular fractions, several intact cell systems are nowadays available. This review discusses the available intestinal in vitro methods to study drug metabolism. The advantages and limitations of intact cell systems (isolated intestinal perfusion, everted sac, Ussing chamber preparations, biopsies, precision-cut slices, primary cells), subcellular fractions (S9 fractions, microsomes) and intestinal cell lines (caco-2, LS180 cells amongst others) are discussed. Their applicability to different species and to study phase I and II metabolism/transport and drug-drug interactions are summarized. Furthermore, causes of variation within and between methods are discussed and metabolic rates obtained with different methods are compared. Whereas subcellular fractions and cell lines are efficient methods to study mechanistic aspects of drug metabolism at the enzyme level, the isolated intestinal perfusion, everted sac and Ussing chamber appear particularly useful for studying drug metabolism of rapidly metabolised drugs and interactions with transporters. Biopsies, precision-cut slices and primary cells seem all appropriate to study induction and metabolism of slowly metabolised drugs.

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Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats

Cited by 14 publications

References 31 publications

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia‐Induced Malnutrition in Mice

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia‐Induced Malnutrition in Mice

Malnutrition impairs alveolar fluid clearance in rat lungs

In Vitro Methods to Study Intestinal Drug Metabolism

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