Studies on glucose synthesis in rat kidney cell suspensions

Guder, W. G.; Siess, Elmar A.; Wieland, O.; Schwarz, Barry E.; Stukowski, Barbara

doi:10.1016/0014-5793(69)80088-8

Cited by 10 publications

(7 citation statements)

References 4 publications

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“…Thus the stimulating effect of fatty acids on glucose formation from lactate could be explained by the observed decrease in pyruvate dehydrogenase activity thus sparing substrate for glucose formation. The observation that oleate [7] and acetate [24] are much weaker stimulators of gluconeogenesis in the presence of high amounts of pyruvate is also in accordance with this concept since pyruvate counteracts the action of oleate on pyruvate dehydrogenase inactivation. On the other hand observations from perfused liver experiments [6] indicate a more complex relationship between fatty acid oxidation and gluconeogenesis, since oleate and acetate can stimulate glucose formation from lactate even under situations where all lactate taken up is converted to glucose (and probably no lactate is oxidized via pyruvate dehydrogenase).…”

Section: Pyruvate Dehydrogenase and Gluconeogenesissupporting

confidence: 68%

“…Earlier experiments had shown that acetate was able to mimic the effects of oleate on renal metabolism [24]. This was confirmed by the determination of pyruvate dehydrogenase in isolated rat kidney tubules.…”

Section: Acetatementioning

confidence: 68%

“…Pyruvate dehydrogenase may therefore be the metabolic step where fatty acids can control glucose oxidation and thereby determine the energy fuels of the kidney cortex and probably the outer medulla [44]. The crucial importance of arterial fatty acids in regulation of kidney cortex pyruvate dehydrogenase has recently been confirmed in studies on metabolic acidosis [45] where it was shown that free-fatty acid levels determine the state of kidneycortex pyruvate dehydrogenase independent from acid-base metabolism which had been shown before to regulate renal gluconeogenesis [46].…”

Section: Physiological Aspects Of Pyruvate Dehydrogenase Interconversmentioning

confidence: 98%

“…The results with 20 mM pyruvate were unexpected, since pyruvate was shown to be a potent activator of pyruvate dehydrogenase in liver [25], adipose tissue [24] and of pyruvate oxidation in heart mitochondria [29]. Since pyruvate dehydrogenase activity after pyruvate a t 45min was lower than after 15 min and lower than after incubation without any substrate it was suggested that changes in pyruvate dehydrogenase activity might have occurred before the first sample was taken.…”

Section: Pyruvatementioning

confidence: 99%

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Metabolism of Isolated Kidney Tubules

Guder

Wieland

1974

European Journal of Biochemistry

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Pyruvate dehydrogenase activity was measured in extracts of isolated kidney cortex tubules, prepared by collagenase treatment. The measured activities were comparable to those described previously for whole kidney homogenates.Incubation of tubules in vitro in the absence of exogenous substrates led to a steady increase in enzyme activity over 30 min. This increase was not significantly changed by the addition of several gluconeogenic substrates including lactate, glutamine, glutamate, glycerol, fructose and malate. 1 mM oleate, 5 mM acetate and 20 mM 2-oxoglutarate however, prevented this increase completely. I n contrast, glucose and dihydroxyacetone accelerated the activation of pyruvate dehydrogenase during incubation in vitro. 20 mM pyruvate very rapidly activated pyruvate dehydrogenase with a following decrease below the activity of control experiments without substrate. 1 mM oleate and 20 mM 2-oxoglutarate counteracted the increase in pyruvate dehydrogenase activity caused by glucose and dihydroxyacetone and had no effect in the presence of 20 mM pyruvate.Determination of the inactive part of pyruvate dehydrogenase after addition of purified pyruvate dehydrogenase phosphatase revealed that all changes observed were probably caused by enzymatic interconversion of pyruvate dehydrogenase.The results are compared with previously published observations on the regulationlof pyruvate dehydrogenase in vivo and confirm the role of fatty acids in the regulation of kidney ,cortex pyruvate metabolism. Enzymes. Pyruvate dehydrogenase (EC 1.2.4.1) ; Arylamine acetyltransferase (EC 2.3.1.5). and kidney cortex [5,7] the mechanism by which fatty acids depressed pyruvate oxidation was a matter of speculation. Inhibition of pyruvate dehydrogenase by increased levels of acetyl-CoA [4] and an increase in reduced nicotinamide-adenine dinucleotide have been discussed as possible metabolic mediators of the action of fatty acids. Although these mechanisms have been shown to operate in isolated mitochondria [S] and with purified enzyme preparations [9], their physiological importance was hard to prove in whole cells since intracellular compartmentalization of metabolites and cofactors prevented $ a n exact interpretation of measured overall levels.The

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Section: Pyruvate Dehydrogenase and Gluconeogenesissupporting

confidence: 68%

Section: Acetatementioning

confidence: 68%

Section: Physiological Aspects Of Pyruvate Dehydrogenase Interconversmentioning

confidence: 98%

Section: Pyruvatementioning

confidence: 99%

See 2 more Smart Citations

Metabolism of Isolated Kidney Tubules

Guder

Wieland

1974

European Journal of Biochemistry

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“…Kidney cortex segments were prepared essentially by the method of Guder et al [6] using a 30 mesh sieve. 125 mg segments were incubated in 2 ml of the phosphate-salts buffer of Krebs et al [7] for 2 hr at * This work was supported by U.S. Public Health Service Grant no.…”

Section: Methodsmentioning

confidence: 99%