Characteristics of glutamine metabolism by rat kidney tubules: a carbon and nitrogen balance

1979 ◽  
Vol 57 (4) ◽  
pp. 346-356 ◽  
Author(s):  
Patrick Vinay ◽  
Guy Lemieux ◽  
André Gougoux
Keyword(s):  
Rat Kidney ◽  
Glucose Production ◽  
Glutamine Metabolism ◽  
Kidney Tubules ◽  
Total Oxidation ◽  
Physiological Concentration ◽  
Prolonged Incubation ◽  
Carbon Chains ◽  
Glucose Synthesis

The metabolism of glutamine by a suspension of rat kidney tubules was studied in vitro. The influence of duration of incubation, glutamine concentration, and metabolic state of the donor animals was investigated. The relative importance of glucose synthesis, amino acid production, and oxidation to CO2 was estimated by drawing a complete balance of the nitrogens and the carbon chains of the extracted glutamine. It was found that the initial (first 15 min) rate of glutamine utilization was significantly greater than the subsequent rate due to an initial, but transient, extracellular accumulation of glutamate. This phenomenon was suppressed when a small amount of glutamate was added to the incubation medium. Glucose production constitutes the major fate for glutamine metabolism. No net oxidation of glutamine could be detected with 1 mM glutamine during the first 30 min. However, glutamine oxidation becomes significant after prolonged incubation (16% at 120 min). The metabolic fate of glutamine differs when 5 or 10 mM are presented to the tubules, glutamate production and oxidation to CO2 becoming more important. Metabolic acidosis or a 48-h fast increases glutamine extraction and enhances its utilization towards glucose synthesis while they depress glutamate accumulation and oxidation to CO2. Metabolic alkalosis has the opposite effect. It is concluded that the metabolism of glutamine in vitro is dependent on the conditions of the study. Furthermore, total oxidation to CO2 is not a major fate for glutamine metabolism at physiological concentration and is not enhanced by acidosis in the rat kidney in vitro.

EFFECTS OF PHENFORMIN AND HYPOGLYCIN ON GLUCONEOGENESIS OF RAT TISSUES

1966 ◽  
Vol 44 (1) ◽  
pp. 27-33 ◽  
Author(s):  
S. J. Patrick
Keyword(s):  
Rat Kidney ◽  
Glucose Production ◽  
Hypoglycemic Agents ◽  
Rat Tissues ◽  
Atp Levels ◽  
Liver Slices

The hypoglycemic agents hypoglycin A and phenformin lower the ATP levels of slices of rat kidney and liver in vitro. These agents, as well as dinitrophenol, interfere with glucose production by kidney and liver slices in the presence of pyruvate or of various intermediate compounds of glycolysis. There is evidence that the activities of fructose-1,6-diphosphatase and glucose-6-phosphatase may be indirectly affected by these agents.

scholarly journals A role for bicarbonate in the regulation of mammalian glutamine metabolism

1979 ◽  
Vol 184 (3) ◽  
pp. 599-606 ◽  
Author(s):  
G Baverel ◽  
P Lund
Keyword(s):  
Rat Kidney ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Complete Oxidation ◽  
Kidney Tubules ◽  
Acid Base Balance ◽  
Acid Base ◽  
Rat Kidney Cortex ◽  
Base Balance

1. The concentration of HCO3- (independent of any change of pH) exerts different effects on glutamine metabolism in rat kidney-cortex tubules, hepatocytes and enterocytes.2. In kidney tubules HCO3- (10.5-50 MM) has no effect on glutaminase (EC 3.5.1.2), whereas glutamate dehydrogenase (EC 1.4.1.3) is inhibited as HCO3- concentration is increased. The result is that flux through the entire glutamate-to-glucose pathway is inhibited by increasing HCO3- concentrations. A large proportion (more than 30%) of the glutamine removed undergoes complete oxidation. 3. In hepatocytes, and to a smaller extent in enterocytes, HCO3- is an accelerator of glutaminase. Synthesis of glucose and urea from glutamine in hepatocytes increases as HCO3- concentration is increased. Calculations show that fumarate, formed via aspartate aminotransferase and arginino-succinate lyase, is the precursor of the glucose. There is no complete oxidation of the carbon skeleton of glutamine in hepatocytes. 4. Leucine at near-physiological concentrations (0.1-1 mM) is an accelerator of glutaminase in hepatocytes, but not in kidney tubules or in enterocytes. 5. The results are discussed in relation to regulation of acid/base balance in vivo.

Glucocorticoid stimulation of Na-K-ATPase in superfused distal segments of kidney tubules in vitro

1982 ◽  
Vol 243 (5) ◽  
pp. F463-F470 ◽  
Author(s):  
B. M. Rayson ◽  
I. S. Edelman
Keyword(s):  
Atpase Activity ◽  
Time Course ◽  
Rat Kidney ◽  
Maximal Effect ◽  
Kidney Tubules ◽  
Response Data ◽  
The One ◽  
Induced Changes

The ability of glucocorticoids to regulate Na-K-ATPase activity directly was assessed in separated rat kidney tubules derived from the distal nephron. These tubules were superfused under sterile conditions and maintained in a viable condition for at least 24 h in a newly devised apparatus. Viability was assessed by measuring O2 consumption, protein/DNA ratios, and Na-K-ATPase and Mg-ATPase activities. At a concentration of 10(-8) M, dexamethasone elicited a 27% increase in tubular Na-K-ATPase activity in 6 h and a 32% increase in 24 h. In a separate series, assayed at 24 h, the maximal effect was obtained at a dexamethasone concentration of less than 10(-8) M, and by inspection half-maximal stimulation was obtained at approximately 10(-9) M. At a concentration of 10(-7) M, 17 beta-estradiol, testosterone, progesterone, and deoxycorticosterone acetate had no significant effect on tubular Na-K-ATPase activity. These results as well as the time-course and dose-response data imply that the response is mediated by the glucocorticoid receptor pathway. Since the magnitude of response in vitro was similar to the one obtained after injection of dexamethasone in vivo, much if not all of the action appears to be direct and independent of glucocorticoid-induced changes in the filtered Na+ load.

Organic mercurial diuresis: Inhibition of glutamine utilization in the acidotic rat

1979 ◽  
Vol 57 (3) ◽  
pp. 227-234
Author(s):  
Louise Passerini ◽  
T. C. Welbourne
Keyword(s):  
Glucose Production ◽  
Dry Weight ◽  
Glutamine Metabolism ◽  
Sodium Reabsorption ◽  
Active Sodium ◽  
Reduced Rate ◽  
Glutamine Uptake ◽  
Organic Mercurials ◽  
Isolated Kidneys

Organic mercurials inhibit mitochondrial glutamine metabolism in vitro while metabolic acidosis, a condition in which the predominant renal fuel is glutamine, potentiates mercurial diuresis. The following studies were undertaken to determine whether potentiation of diuresis reflects mercurial inhibition of glutamine utilization.(1) All three mercurials employed (mersalyl, chlormerodrin, and p-chloromercuribenzoate) are diuretics in the rat and this effect was potentiated by NH4Cl.(2) Despite reabsorbing less sodium, mercurial-treated rats had lower kidney ATP content (4.35 ± 0.26 and 3.85 ± 0.43 μmol/g dry weight (mercurial plus NH4Cl)) than did controls (4.95 ± 0.31 and 4.87 ± 0.39 μmol/g dry weight (NH4Cl)).(3) Isolated kidneys from NH4Cl and NH4Cl plus mercurial treated rats were perfused with 1 mML-[U-14C]glutamine to determine rates of extraction and oxidation. Mercurial-treated acidotic rat kidneys had a reduced rate of glutamine uptake (40.8 ± 7.4 vs. 64.8 ± 5.8 μmol/h. per kidney), a diminished rate of glutamine conversion to CO2 (14.8 ± 3.6 vs. 26.4 ± 5.2 μmol/h per kidney), and a reduction in glucose production (16 ± 5 vs. 27 ± 4 μmol/h per kidney). These results are consistent with an effect of organic mercurials upon glutamine utilization, limiting ATP availability, and thereby reducing tubular active sodium reabsorption.

scholarly journals Stimulation of glutamine metabolism by 3-aminopicolinate in isolated dog kidney-cortex tubules

1983 ◽  
Vol 210 (2) ◽  
pp. 483-487 ◽  
Author(s):  
D Durozard ◽  
G Baverel
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Kidney Tubules ◽  
Direct Stimulation ◽  
Dog Kidney ◽  
Glucose Synthesis ◽  
Isolated Dog Kidney ◽  
Gluconeogenic Substrates ◽  
Stimulation Of

1. The effects of 3-aminopicolinate, a known hyperglycaemic agent in the rat, on glutamine metabolism were studied in isolated dog kidney tubules. 2. 3-Aminopicolinate greatly stimulated glutamine (but not glutamate) removal and glutamate accumulation from glutamine as well as formation of ammonia, aspartate, lactate, alanine and glucose. 3. The increased accumulation of aspartate from glutamine and glutamate, and the inhibition of glucose synthesis from various non-nitrogenous gluconeogenic substrates, as well as the increased accumulation of malate from succinate, support the proposal that 3-aminopicolinate is an inhibitor rather than a stimulator of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in dog kidney tubules. 4. With glutamine as substrate, the increase in flux through glutamate dehydrogenase (EC 1.4.1.3) could not explain the large increase in glutamine removal caused by 3-aminopicolinate. 5. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by 3-aminopicolinate did not prevent the acceleration of glutamine utilization. 6. These data are consistent with a direct stimulation of glutaminase (EC 3.5.1.2) by 3-aminopicolinate in dog kidney tubules.

scholarly journals Serine synthesis by an isolated perfused rat kidney preparation

1985 ◽  
Vol 230 (2) ◽  
pp. 303-311 ◽  
Author(s):  
R C Scaduto ◽  
E J Davis
Keyword(s):  
Aspartate Aminotransferase ◽  
Essential Role ◽  
Rat Kidney ◽  
Glucose Production ◽  
Complete Inhibition ◽  
Maximal Rate ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Glucose Synthesis

The isolated perfused rat kidney was shown to synthesize serine from aspartate or glutamate, both of which are also precursors of glucose. The major products of aspartate metabolism were ammonia, serine, glutamate, glucose, glutamine and CO2. Perfusion of kidneys with aspartate in the presence of amino-oxyacetate resulted in a near-complete inhibition of aspartate metabolism, illustrating the essential role of aspartate aminotransferase in the metabolism of this substrate. Radioactivity from 14C-labelled aspartate and from 14C-labelled glycerol was incorporated into serine and glucose. Production of both glucose and serine from aspartate was suppressed in the presence of 3-mercaptopicolinic acid. These data provide evidence for the operation of the phosphorylated and/or non-phosphorylated pathway for serine production to the presence of 3-mercaptopicolinic acid. This is explained by simultaneous glycolysis. The rate of glucose production, but not that of serine, was greater in kidneys perfused with glutamate or with aspartate plus glycerol than the rates obtained by perfusion with aspartate alone. These data are taken to suggest that serine synthesis occurred at a near-maximal rate, and that the capacity of the kidney for serine synthesis from glucose precursors is lower than that for glucose synthesis.

Effect of UUO on D1aR expression reveals a link among dopamine, transforming growth factor-β, and nitric oxide

2004 ◽  
Vol 286 (3) ◽  
pp. F509-F515 ◽  
Author(s):  
Joshua M. Stern ◽  
Jie Chen ◽  
Randi B. Silver ◽  
Dix P. Poppas ◽  
E. Darracott Vaughan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Transforming Growth Factor Β ◽  
Kidney Tubules ◽  
Concurrent Treatment ◽  
Normal Rat

Interactions between transforming growth factor-β (TGF-β) and nitric oxide (NO) are important in the pathophysiology of unilateral ureteral obstruction (UUO). Dopamine (DA) is a vasoactive renal mediator active at the D1A receptor (D1AR), which has not been studied in UUO; therefore, we examined the interactions among DA, TGF-β, and NO in UUO. In vivo, UUO was carried out in rats with or without concurrent treatment with 1D11, a monoclonal antibody to TGF-β, for 14 days. In vitro, NRK-52E cells (normal rat kidney tubules) were treated with DA, and NO and TGF-β release were examined. UUO resulted in a 70% decrease in the expression of renal D1AR, confirmed by both Western blot analysis and immunohistochemistry. 1D11 treatment restored expression to 60% of control values. DA treatment decreased NRK-52E release of TGF-β by 80%; conversely, DA significantly increased NO release from NRK-52E cells. These results suggest that DA modulates the release of cytokines, which are involved in the fibrotic and apoptotic sequelae of UUO, and that these effects are independent of DA's known vasoactive properties.

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.

Electron microscopic study of the membrane glycoproteins in the rat kidney after cisplatin treatment

1989 ◽  
Vol 47 ◽  
pp. 912-913
Author(s):  
S.K. Aggarwal
Keyword(s):  
Alkaline Phosphatase ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Kidney Tissue ◽  
Membrane Glycoproteins ◽  
Electron Microscopic ◽  
Before And After ◽  
Interstrand Cross Links ◽  
Cross Links

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.

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