On the stimulation of gluconeogenesis by l-Lysine in isolated rat kidney cortex tubules

Friedrichs, Dagmar

doi:10.1016/0304-4165(75)90007-0

Cited by 14 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The malate–aspartate shuttle has largely studied in cancer cells, and some suggest that the glucose fermentation (ie, Warburg effect) is a secondary consequence of saturation of the shuttle. 101 The malate–aspartate shuttle can be stimulated by an increase in glutamine uptake, 102 , 103 which we observed ( Figure 6 ). The key enzymes, oxaloacetate transaminase (GOT) and malate dehydrogenase (MDH) activate the shuttle by forming a complex with acetylation 104 and we observed an increase in Got mRNA expression.…”

Section: Discussionsupporting

confidence: 62%

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake

et al. 2023

View full text Add to dashboard Cite

In this study, novel methods were developed which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague-Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to 4.0% NaCl diet. In addition, targeted mRNA expression analysis of cortical segments was performed. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. A novel finding was the increased expression of glycolysis-related genes in Cx and isolated proximal tubular segments in response to a HS diet, consistent with increased release of pyruvate and lactate from the kidney to the renal venous blood. Glycolytic production of NADH is used in either the production of lactate or transport via the malate-aspartate shuttle for oxidation and energy production in mitochondria. Aerobic glycolysis (e.g., Warburg-effect) may therefore contribute to the needed increase in cellular energy in normal rats fed a HS diet. The study provides evidence that kidney metabolism responds to a HS diet enabling enhanced energy production while protecting from oxidative stress and injury.

show abstract

Section: Discussionsupporting

confidence: 62%

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Warburg effect) is a secondary consequence of saturation of the shuttle 84 . The malate-aspartate shuttle can be stimulated by an increase in glutamine uptake 85, 86 which we observed ( Figure 7 ). The key enzymes, oxaloacetate transaminase (GOT) and malate dehydrogenase (MDH) activate the shuttle by forming a complex with acetylation 87 and we observed an increase in GOT mRNA expression.…”

Section: Discussionsupporting

confidence: 61%

Metabolic responses of normal rat kidneys to a high salt intake

Shimada

Yang

Kurth

et al. 2023

Preprint

View full text Add to dashboard Cite

In the present study, novel methods were developed which allowed continuous (24/7) measurement of blood pressure (BP) and renal blood flow (RBF) in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. The study determined the effects of a high salt (HS) diet upon whole kidney O2 consumption and the metabolomic profiles of normal Sprague Dawley (SD) rats. A separate group of rats was studied to determine changes in the cortex (Cx) and outer medulla (OM) tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to a 4.0% NaCl diet. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. Increased glycolysis was evident with the elevation of mRNA expression encoding key glycolytic enzymes and release of pyruvate and lactate from the kidney in the renal venous blood. Glycolytic production of NADH is used in either the production of lactate or oxidized via the malate aspartate shuttle. Aerobic glycolysis (e.g., Warburg-effect) may account for the needed increase in cellular energy. The study provides interesting and provocative new data of how normal kidneys respond to a HS diet and guides us toward deeper mechanistic studies examining the effects of a HS diet upon kidney metabolism.

show abstract

“…This is in agreement with data for rat liver (Berry et al, 1973;Werner and Berry, 1974) indicating that transport of reducing equivalents from cytosol into mitochondria limits the rate of glucose formation from glycerol as the sole substrate. According to Friedrichs (1975), compounds that can form glutamate like ammonium and several amino acids stimulate gluconeogenesis from lactate in isolated rat renal tubules through an increased provision of glutamate and, thereby, aspartate, resulting in an activation of malate-aspartate shuttle. Similarly, it has been recently shown that asparagine stimulates glucose formation from lactate in isolated hepatocytes (Efthivoulou et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

Fatty acids and glycerol or lactate are required to induce gluconeogenesis from alanine in isolated rabbit renal cortical tubules

1999

View full text Add to dashboard Cite

In isolated rabbit renal cortical tubules, glucose synthesis from 1 mM alanine is negligible, while the amino acid is metabolized to glutamine and glutamate. The addition of 0.5 mM octanoate plus 2 mM glycerol induces incorporation of [U-14C]alanine into glucose and decreases glutamine synthesis, whereas oleate and palmitate in the presence of glycerol are less potent than octanoate. Gluconeogenesis is also significantly accelerated when glycerol is substituted by lactate. In view of an increase in 14CO2 fixation and elevation of both cytosolic and mitochondrial NADH/NAD+ ratios, the activation of glucose formation from alanine upon the addition of glycerol and octanoate is likely due to (i) stimulation of pyruvate carboxylation, (ii) increased availability of NADH for glyceraldehyde-3-phosphate dehydrogenase and (iii) elevation of mitochondrial redox state causing a diminished provision of ammonium for glutamine synthesis. The induction of gluconeogenesis in the presence of alanine, glycerol and octanoate is not related to cell volume changes. The results presented in this paper show the importance of free fatty acids and glycerol for regulation of renal gluconeogenesis from alanine. The possible physiological significance of the data is discussed.

show abstract

On the stimulation of gluconeogenesis by l-Lysine in isolated rat kidney cortex tubules

Cited by 14 publications

References 29 publications

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake

Metabolic responses of normal rat kidneys to a high salt intake

Fatty acids and glycerol or lactate are required to induce gluconeogenesis from alanine in isolated rabbit renal cortical tubules

Contact Info

Product

Resources

About