The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex

Longshaw, Ian D.; Pogson, C. I.

doi:10.1172/jci107037

Cited by 38 publications

(20 citation statements)

References 27 publications

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“…By contrast, it is conceivable that corticosterone, whose circulating concentration was elevated in our diabetic Zucker rats like in a previous study by other authors (39), was responsible, at least in part, for the stimulation of renal glucose synthesis in our diabetic rats. Indeed, glucocorticoids have been shown to upregulate (1) the expression of the phosphoenolpyruvate carboxykinase gene (33,40,41), (2) the enzymatic activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (35,(42)(43)(44), and (3) the capacity of rat renal cortical slices to synthesize glucose from pyruvate and succinate (45) but not the expression of the glutaminase gene (41) or the activity of fructose-1,6-bisphosphatase (43) in the rat kidney. In agreement with the last observations, the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase but not that of fructose-1,6-bisphosphatase were stimulated in renal proximal tubules of lean Zucker rats that were treated with dexamethasone ( Table 5).…”

Section: Factors Responsible For Long-term Stimulation Of Renal Glucomentioning

confidence: 99%

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Eid

Bodin²,

Ferrier³

et al. 2006

Journal of the American Society of Nephrology

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Recent studies indicate that renal gluconeogenesis is substantially stimulated in patients with type 2 diabetes, but the mechanism that is responsible for such stimulation remains unknown. Therefore, this study tested the hypothesis that renal gluconeogenesis is intrinsically elevated in the Zucker diabetic fatty rat, which is considered to be an excellent model of type 2 diabetes. For this, isolated renal proximal tubules from diabetic rats and from their lean nondiabetic littermates were incubated in the presence of physiologic gluconeogenic precursors. Although there was no increase in substrate removal and despite a reduced cellular ATP level, a marked stimulation of gluconeogenesis was observed in diabetic relative to nondiabetic rats, with near-physiologic concentrations of lactate (38%), glutamine (51%) and glycerol (66%). This stimulation was caused by a change in the fate of the substrate carbon skeletons resulting from an increase in the activities and mRNA levels of the key gluconeogenic enzymes that are common to lactate, glutamine, and glycerol metabolism, i.e., mainly of phosphoenolpyruvate carboxykinase and, to a lesser extent, of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Experimental evidence suggests that glucocorticoids and cAMP were two factors that were responsible for the long-term stimulation of renal gluconeogenesis observed in the diabetic rats. These data provide the first demonstration in an animal model that renal gluconeogenesis is upregulated by a long-term mechanism during type 2 diabetes. Together with the increased renal mass (38%) observed, they lend support to the view so far based only on in vivo studies performed in humans that renal gluconeogenesis may be stimulated by and crucially contribute to the hyperglycemia of type 2 diabetes.

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Section: Factors Responsible For Long-term Stimulation Of Renal Glucomentioning

confidence: 99%

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Eid

Bodin²,

Ferrier³

et al. 2006

Journal of the American Society of Nephrology

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“…The classic study of Girard et al [4] would also suggest that the rising glucagon level at birth is a major regulator of this enzy matic shift. In contrast, renal PEPCK activa tion and renal gluconeogenesis after birth seem more closely allied to acidosis as in the adult animal [2,10,11]. Further, perinatal treatment with glucocorticoids has been shown by some workers to induce a slow increase in PEPCK activity in both the liver and kidney of the rat neonate, while others have not been able to demonstrate a clear influence of glucocorticoids on adult or fetal liver PEPCK [5,15,26,29].…”

Section: Discussionmentioning

confidence: 98%

“…Although the factors controlling the induction of this criti cal enzyme have not been explored fully in the neonate, they arc different in the adult kidney and liver. Glucocorticoids, known growth-retarding agents [23,27], are potent stimulators of renal PEPCK activity in the adult rat [5,6,10,11], but the response of hepatic PEPCK to these steroids varies [3,5,10,21,25], When glucocorticoids do increase PEPCK activity, the induction process exhib its different kinetics in the kidney and liver [ 10].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Dexamethasone and Surgically Induced Intrauterine Growth Retardation on Renal and Hepatic Levels of Phosphoenolpyruvate Carboxykinase in the Rat

Levitsky¹,

Edidin²,

Menella³

et al. 1986

Neonatology

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Renal and hepatic levels of the rate-limiting gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were determined in control and intrauterine growth-retarded rate neonates and dams. Dexamethasone and surgically induced intrauterine growth retardation (IUGR) resulted in an elevation of neonatal renal PEPCK activity, but did not affect hepatic PEPCK levels. In the dam, glucocorticoid administration resulted in an increase in renal PEPCK, but did not affect the hepatic enzyme. We have demonstrated that, unlike the hepatic enzyme, renal PEPCK could potentially contribute to gluconeogenesis in utero, since dexamethasone administration significantly increased renal PEPCK at birth. This study confirms the hypothesis that hepatic and renal PEPCK activities are regulated independently in both the adult and neonatal animal.

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“…1), which is not metabolized, and of citrate (10 Proposed role of phenomenon in acid-base-induced changes in renal substrate levels. Nagata and Rasmussen (9) the levels of PEP in very acute acid-base disturbances makes it unlikely that the changes in renal substrate levels at this early stage are the result of altered activity of PEP carboxykinase, an explanation that has been invoked to account for reduction in substrate levels later in acidosis when increased activity of this enzyme develops (22,23).…”

Section: Discussionmentioning

confidence: 99%

pH and Bicarbonate Effects on Mitochondrial Anion Accumulation

Simpson¹,

Hager²

1979

J. Clin. Invest.

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A B S T R A C T Mitochondria from rabbit and dog renal cortex were incubated with 1 mM "4C-weak acid anions in media containing low (10 mM) or high (40 mM) concentrations of bicarbonate and the steady-state accumulation of labeled anion in the matrix was measured. In the absence of an energy source, no concentration of 14C-anion in the mitochondrial matrix space was present, but the anion concentration was significantly higher at low-than at high-bicarbonate concentration. Addition of an energy source, usually ascorbate plus tetramethyl-p-phenylenediamine, led to increases in matrix space anion levels and to accentuation of the difference in anion uptake between low-and highbicarbonate media, so that two to four times as much anion was present at low-than at high-bicarbonate concentrations. The anions affected included substrates for which inner membrane carriers are present in mitochondria, such as citrate, a-ketoglutarate, malate, and glutamate, as well as substances which diffuse passively across the inner membrane such as acetate and formate. When a nonbicarbonate medium buffered with Hepes was used, pH change did not alter anion uptake although anion concentrations exceeding those in the medium still developed when an energy source was present. The difference in mitochondrial anion accumulation between low-and high-bicarbonate levels diminished with decreasing temperature or with increasing anion concentration in the medium. Estimation of intramitochondrial pH with [14C]5,5-dimethyloxazolidine-2,4-dione showed that the pH gradient Parts of this study were presented at

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The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex

Cited by 38 publications

References 27 publications

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

The Effect of Dexamethasone and Surgically Induced Intrauterine Growth Retardation on Renal and Hepatic Levels of Phosphoenolpyruvate Carboxykinase in the Rat

pH and Bicarbonate Effects on Mitochondrial Anion Accumulation

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