PPAR-γ-independent inhibitory effect of rosiglitazone on glucose synthesis in primary cultured rabbit kidney-cortex tubules

Therapeutic effect of rosiglitazone has been reported to result from an improvement of insulin sensitivity and inhibition of glucose synthesis. As the latter process occurs in both liver and kidney cortex the aim of this study was to elucidate the rosiglitazone action on glucose formation in both tissues. Primary cultured cells of both liver and kidney cortex grown in defined medium were use throughout. To identify the mechanism responsible for drug-induced changes, intracellular gluconeogenic intermediates and enzyme activities were determined. In contrast to hepatocytes, the administration of a 10 µmol/L concentration of rosiglitazone to renal tubules resulted in about a 70% decrease in the rate of gluconeogenesis, accompanied by an ~75% decrease in alanine utilization and a 35% increase in lactate synthesis. The effect of rosiglitazone was not abolished by GW9662, the PPAR-γ irreversible antagonist, indicating that this action is not dependent on PPAR-γ activation. In view of rosiglitazone-induced changes in gluconeogenic intermediates and a diminished incorporation of 14CO2 into pyruvate, it is likely that the drug causes a decline in flux through pyruvate carboxylase and (or) phosphoenolpyruvate carboxykinase. It is likely that the hypoglycemic action of rosiglitazone is PPAR-γ independent and results mainly from its inhibitory effects on renal gluconeogenesis.

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Diabetes-induced changes in glucose synthesis, intracellular glutathione status and hydroxyl free radical generation in rabbit kidney-cortex tubules

Molecular and Cellular Biochemistry ◽

10.1023/b:mcbi.0000028742.83086.43 ◽

2004 ◽

Vol 261 (1) ◽

pp. 91-98 ◽

Cited By ~ 32

Author(s):

K. Winiarska ◽

J. Drozak ◽

M. Wegrzynowicz ◽

T. Fraczyk ◽

J. Bryla

Keyword(s):

Free Radical ◽

Rabbit Kidney ◽

Kidney Cortex ◽

Free Radical Generation ◽

Hydroxyl Free Radical ◽

Glutathione Status ◽

Intracellular Glutathione ◽

Glucose Synthesis ◽

Radical Generation ◽

Induced Changes

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Assessment of the Protective Effect of Lepidium sativum against Aluminum-Induced Liver and Kidney Effects in Albino Rat

BioMed Research International ◽

10.1155/2019/4516730 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Maha Jameal Balgoon

Keyword(s):

Structural Changes ◽

Lepidium Sativum ◽

Albino Rats ◽

Renal Tubules ◽

Albino Rat ◽

Antioxidant Power ◽

Superior Effect ◽

Ferric Reducing Antioxidant Power ◽

Liver And Kidney ◽

Induced Changes

Background and Objectives. Environmental pollution with the different Aluminum (Al) containing compounds has been increased. Liver and kidney are two vital organs targeted by Al accumulation. The aim of this study was to assess the possible protective and curative effects of Lepidium sativum Linn (LS) against Al-induced impairment of liver and kidney in albino rat and to explore the mechanism behind this effect. Materials and Methods. This experimental animal-based study included fifty albino rats divided into five groups, the control, LS-treated (20 mg/kg), AlCl3-treated (10 mg/kg), AlCl3 then LS, and AlCl3 plus LS-treated, simultaneously for 8 weeks. At the end of the experiment, hepatic and renal functions as well as the biomarkers of antioxidants activities were assessed in the serum. Both liver and kidney were dissected out and histopathologically examined. Results. This study showed that administration of AlCl3 caused a significant (p<0.05) reduction in rats body weight. It significantly increased serum AST, ALT, ALP, bilirubin, urea, and creatinine levels and decreased total protein and albumin. AlCl3 significantly reduced enzymatic (catalase), nonenzymatic (reduced glutathione), and ferric reducing antioxidant power (FRAP) in the serum. Histopathologically, it induced necrosis and degeneration of hepatocytes, glomeruli, and renal tubules. Administration of LS after or along with AlCl3 significantly restored the serum biomarkers of liver and kidney functions to their near-normal levels and had the ability to overcome Al-induced oxidative stress and preserved, to some extent, the normal hepatic and renal structure. The coadministration of LS had a superior effect in alleviating Al-induced changes. Conclusion. Exposure to AlCl3 induced a set of functional and structural changes in the liver and kidney of rats evident through both biochemical and histopathological assessment. The antioxidant activity of LS seeds mediated a protective and curative effect of LS against such changes. Further study through a rigorous clinical trial to prove LS activity on human is recommended.

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Proinsulin C-peptide potentiates the inhibitory action of insulin on glucose synthesis in primary cultured rabbit kidney-cortex tubules: Metabolic studies

Biochemistry and Cell Biology ◽

10.1139/bcb-2013-0074 ◽

2014 ◽

Vol 92 (1) ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Michal Usarek ◽

Adam Konrad Jagielski ◽

Paulina Krempa ◽

Anna Dylewska ◽

Anna Kiersztan ◽

...

Keyword(s):

Inhibitory Action ◽

Primary Cultures ◽

Rabbit Kidney ◽

Kidney Cortex ◽

C Peptide ◽

Renal Tubular Cells ◽

Regulatory Enzymes ◽

Glucose Synthesis ◽

Renal Tubular ◽

Fructose 1,6 Bisphosphate

Effects of equimolar concentrations of proinsulin C-peptide and insulin on glucose synthesis were studied in primary cultures of rabbit kidney-cortex tubules grown in the presence of alanine, glycerol, and octanoate. The rhodamine-labeled C-peptide entered renal tubular cells and localized in nuclei, both in the presence and absence of insulin; preincubations with the unlabeled compound inhibited internalization. C-peptide did not affect glucose formation when added alone but potentiated the inhibitory action of insulin by about 20% due to a decrease in flux through glucose-6-phosphate isomerase (GPI) and (or) glucose-6-phosphatase (G6Pase). GPI inhibition was caused by: (i) increased intracellular contents of fructose-1,6-bisphosphate and fructose-1-phosphate, inhibitors of the enzyme and (ii) reduced level of the phosphorylated GPI, which exhibits higher enzymatic activity in the presence of casein kinase 2. A decrease in flux through G6Pase, due to diminished import of G6P by G6P-transporter from the cytoplasm into endoplasmic reticulum lumen, is also suggested. The data show for the first time that in the presence of insulin and C-peptide, both GPI and G6P-ase may act as regulatory enzymes of renal gluconeogenic pathway.

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Indirect immunoselection of late distal cell populations from rabbit kidney cortex

AJP Renal Physiology ◽

10.1152/ajprenal.1986.250.3.f386 ◽

1986 ◽

Vol 250 (3) ◽

pp. F386-F395 ◽

Cited By ~ 1

Author(s):

A. Vandewalle ◽

M. Tauc ◽

F. Cluzeaud ◽

P. Ronco ◽

F. Chatelet ◽

...

Keyword(s):

Cell Suspension ◽

Brush Border ◽

Phosphoenolpyruvate Carboxykinase ◽

High Yield ◽

Rabbit Kidney ◽

Kidney Cortex ◽

Cell Populations ◽

Cortical Cells ◽

Rate Of Oxygen Consumption ◽

Distal Cell

This study describes a method for the separation of distal cell populations based on the sequestration of proximal cells on immunoadsorbent columns (CNBr-activated Sepharose 6MB) bound with three brush-border monoclonal antibodies (S6-Mab). A high yield of isolated cell suspension from rabbit kidney cortex was prepared by mechanical dissociation after perfusion and incubation of the kidneys with 10(-3) M EDTA. The sequestration of the proximal cells was achieved in two sequential chromatographic steps. About 92% of the applied cells were first retained on an S6-Mab column after a 60-min stationary stage and the unbound cells were submitted by direct flow to a second S6-Mab column. In such conditions, 8 X 10(6) cells were recovered when starting with 331 X 10(6) cortical cells. The efficiency of the proximal cell depletion process was confirmed by an 80% decrease in brush-border enzymes, a very low phosphoenolpyruvate carboxykinase activity, and absence of cells bearing long microvilli, as ascertained by electron microscopy. This immunodepleted cell population presented the enzymatical characteristics of cells from the more distal segments. As compared with the initial cell suspension, these cells exhibited higher hexokinase (2.3 times), succinate dehydrogenase (1.5 times), and Na+-K+-ATPase (2.6 times) activities. In addition, adenylate cyclase activities remained sensitive to parathormone, arginine vasopressin, and isoproterenol. The functional capacity of these immunodepleted cells was assessed by an almost complete exclusion of eosin dye, a low Na+ and high K+ intracellular content, and a high respiratory rate of oxygen consumption. In conclusion, this immunoselective process makes it possible to obtain subpopulations of renal cortical cells possessing the main characteristics of the distal, connecting, and collecting cells for physiological and metabolic studies.

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Differential effects of selenium compounds on glucose synthesis in rabbit kidney-cortex tubules and hepatocytes. In vitro and in vivo studies

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2006.11.012 ◽

2007 ◽

Vol 101 (3) ◽

pp. 493-505 ◽

Cited By ~ 13

Author(s):

Anna Kiersztan ◽

Izabela Lukasinska ◽

Anna Baranska ◽

Magdalena Lebiedzinska ◽

Andrzej Nagalski ◽

...

Keyword(s):

In Vivo Studies ◽

Rabbit Kidney ◽

Kidney Cortex ◽

Selenium Compounds ◽

Differential Effects ◽

Glucose Synthesis

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The activities and intracellular distribution of nicotinamide-adenine dinucleotide phosphate-malate dehydrogenase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in rat, guinea-pig and rabbit tissues

Biochemical Journal ◽

10.1042/bj1460329 ◽

1975 ◽

Vol 146 (2) ◽

pp. 329-332 ◽

Cited By ~ 11

Author(s):

D E Saggerson ◽

C J Evans

Keyword(s):

Adipose Tissue ◽

Guinea Pig ◽

Malate Dehydrogenase ◽

Pyruvate Carboxylase ◽

Phosphoenolpyruvate Carboxykinase ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Intracellular Distribution ◽

Kidney Cortex ◽

Carboxylase Activity ◽

Liver And Kidney

1. Measurements are presented of the activity and intracellular distribution of phosphoenolypruvate carboxykinase, pyruvate carboxylase and NADP-malate dehydrogenase in rat, guinea-pig and rabbit liver and kidney cortex, together with previously obtained measurements of these enzymes in adipose tissue. 2. In all three tissues pyruvate carboxylase activity was greatest in the rat and lowest in the rabbit. 3. Guinea pig and rabbit were very similar to each other with respect to the extramitochondrial-mitochondrial distribution of phosphoenolpyruvate carboxykinase in all three tissues. 4. NADP-malate dehydrogenase was present in all three tissues in the rat, present in kidney cortex and adipose tissue in the guinea pig and absent from all tissues examines in the rabbit.

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

Biochemical Journal ◽

10.1042/bj2100483 ◽

1983 ◽

Vol 210 (2) ◽

pp. 483-487 ◽

Cited By ~ 2

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.

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Studies on glucose synthesis by rat liver and kidney cortex slices

Life Sciences ◽

10.1016/0024-3205(66)90297-9 ◽

1966 ◽

Vol 5 (7) ◽

pp. 655-663 ◽

Cited By ~ 12

Author(s):

S.R. Wagle ◽

R.K. Gaskins ◽

Annette Jacoby ◽

J. Ashmore

Keyword(s):

Rat Liver ◽

Kidney Cortex ◽

Liver And Kidney ◽

Glucose Synthesis ◽

Cortex Slices ◽

Kidney Cortex Slices

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Subcellular localization and drug-Induced changes; of rat liver and kidney esterases

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y68-034 ◽

1968 ◽

Vol 46 (2) ◽

pp. 207-212 ◽

Cited By ~ 35

Author(s):

W. S. Schwark ◽

D. J. Ecobichon

Keyword(s):

Rat Liver ◽

Gel Electrophoresis ◽

Esterase Activity ◽

Microsomal Fraction ◽

Starch Gel Electrophoresis ◽

Drug Induced ◽

Liver Esterase ◽

Liver And Kidney ◽

Starch Gel ◽

Induced Changes

The subcellular distribution of the esterases of rat liver and kidney was examined by differential centrifugation followed by quantitative titrimetric analysis, starch-gel electrophoresis, and electron microscopy of the subcellular fractions. The esterases were found primarily in the microsomal fraction of the cell. Soluble or cytoplasmic forms of esterases were also found. These conclusions were substantiated by induction studies with DDT and sodium phenobarbitone. Both drugs were capable of inducing liver esterase activity, DDT being more potent. In contrast to the liver, increased kidney esterase activity was not induced by these compounds.

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