Study of Inhibition of Induction of Phosphoenolpyruvate Carboxykinase by Endotoxin with Radial Immunodiffusion

Rippe, Delfin F.; Berry, L. Joe

doi:10.1128/iai.6.5.766-772.1972

Cited by 23 publications

(9 citation statements)

References 8 publications

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“…The inhibition of hepatic PEPCK seen in intact mice given endotoxin (Fig. 2) is consistent with previous results (5,30) and indicates that the enzyme is a sensitive marker of endotoxin poisoning since a significant inhibition was noted as early as 3 h after treatment. By 6 h after endotoxin administration, PEPCK activity was reduced to approximately 60% of the control value, a level of catalytic activity insufficient to drive the gluconeogenic pathway required in animals subjected to stress (9).…”

Section: Discussionsupporting

confidence: 91%

“…2) further supports the contention that endotoxin affects the glucocorticoid inducibility of this enzyme (13, 29) but does not act directly on the enzyme. Berry and associates have partially characterized the inhibition of steroid induction of several liver enzymes, including tryptophan oxygenase and PEPCK (5,30,31). The results presented in Fig.…”

Section: Discussionmentioning

confidence: 99%

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Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase

McCallum¹,

Seale²,

Stith³

1983

Infect Immun

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Decreased glucocorticoid binding has been observed at a time after endotoxin (3 to 6 h) when imparied liver enzyme induction is known to occur. This study was undertaken to characterize the early time course of hypoglycemia and decreased liver phosphoenolpyruvate carboxykinase (PEPCK) activity in intact and adrenalectomized mice given endotoxin. In addition, altered steroid induction of hepatic PEPCK was examined in adrenalectomized mice given dexamethasone at intervals before and after a median lethal dose of endotoxin. Intact mice demonstrated a dramatic hyperglycemia at 1 h after endotoxin treatment, a response absent in adrenalectomized mice. Plasma glucose levels were significantly reduced from control values at 3 and 6 h posttreatment, with the most pronounced endotoxin-induced hypoglycemia seen in adrenalectomized mice. Hepatic PEPCK activity in intact mice given endotoxin was decreased at 3 and 6 h after treatment, although no change from basal, noninduced levels was seen in poisoned adrenalectomized mice. The increased increment in hepatic PEPCK activity due to fasting of intact control mice was reproduced in adrenalectomized control mice by the administration of dexamethasone. Furthermore, the induction of hepatic PEPCK by dexamethasone was inhibited by 1 h after endotoxin treatment, with enzyme activity falling to basal, noninduced levels by 6 h posttreatment. At these same time intervals after endotoxin treatment, no evidence of histopathology in the liver or adrenal glands was seen. These results coincide with changes in steroid binding seen previously and indicate that endotoxin treatment produces significant alterations in glucocorticoid action at the subcellular or molecular level.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase

McCallum¹,

Seale²,

Stith³

1983

Infect Immun

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“…ticoid-antagonizing factor inhibits glucocorticoid-induced phosphoenolpyruvate carboxykinase, a liver enzyme which controls the rate-limiting step in gluconeogenesis (35,36). Both recombinant IL-1 and recombinant TNF have been shown to induce hypoglycemia in vivo (3,17).…”

Section: Discussionmentioning

confidence: 99%

Differential cytokine induction by doses of lipopolysaccharide and monophosphoryl lipid A that result in equivalent early endotoxin tolerance

1990

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The phenomenon of early endotoxin tolerance, which is induced by sublethal injection of lipopolysaccharide (LPS), results in a protracted period of hyporesponsiveness that is most profound at 3 to 4 days after injection and is marked by reduced cytokine production after a challenge injection of LPS. Early endotoxin tolerance is also induced by the nontoxic LPS derivative monophosphoryl lipid A (MPL), although much more of the monophosphoryl derivative is required to produce a state of tolerance equivalent to that evoked by LPS. In this study, equivalent tolerance-inducing doses of LPS and MPL were tested, and the levels of cytokines induced by LPS and MPL were compared. Although induced levels of colony-stimulating factor were comparable following doses of LPS and MPL that elicited an equivalent state of early endotoxin tolerance, levels of tumor necrosis factor, interleukin-6, and interferon were significantly lower in MPL-injected animals. These results suggest that the lowered toxicity of MPL may be related to its elicitation of significantly lower levels of potentially toxic intermediaries such as tumor necrosis factor, interferon, and interleukin-6.

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“…It has been known for quite some time that induction in vivo by cortisone of PCK enzyme activity in mouse liver was inhibited by endotoxin (26,27). In rats and mice endotoxemia decreased hepatic PCK on the transcriptional level (28,29).…”

Section: Hepatology December 1994mentioning

confidence: 99%

Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of glucokinase gene expression in cultured rat hepatocytes: Regulation of gene transcription and messenger RNA degradation

Christ¹,

Nath²,

Heinrich

et al. 1994

Hepatology

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The influence of recombinant human interleukin-6, the major mediator of the inflammatory response in liver, on the glucagon- and insulin-dependent induction of the phosphoenolpyruvate carboxykinase and glucokinase gene, respectively, was monitored on the level of gene transcription, mRNA abundance and enzyme activity in cultured rat hepatocytes. As control markers of the interleukin-6-induced acute-phase response the mRNA levels of the acute phase proteins alpha 2-macroglobulin and beta-fibrinogen were determined. In cultured rat hepatocytes, recombinant human interleukin-6, added simultaneously with glucagon and insulin, lowered the maximal increase in glucagon-induced phosphoenolpyruvate carboxykinase mRNA levels after 2 hr and the maximal increase in glucokinase mRNA levels after 3 hr to about 30%, respectively. It inhibited the glucagon-induced increase in phosphoenolpyruvate carboxykinase gene transcription and phosphoenolpyruvate carboxykinase enzyme activity, as well as the insulin-induced increases in glucokinase gene transcription and glucokinase enzyme activity. Recombinant human interleukin-6 increased the mRNA levels of the acute-phase proteins alpha 2-macroglobulin and beta-fibrinogen gradually over 4 to 6 hr. Recombinant human interleukin-6, added 2 hr after glucagon or 3 hr after insulin at the maximum of the hormone-induced enzyme mRNA levels, almost doubled the decay rate of phosphoenolpyruvate carboxykinase mRNA and glucokinase mRNA. The results show that interleukin-6 induced the expression of inflammatory proteins and simultaneously inhibited the hormone-induced expression of enzymes of intermediary metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

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Study of Inhibition of Induction of Phosphoenolpyruvate Carboxykinase by Endotoxin with Radial Immunodiffusion

Cited by 23 publications

References 8 publications

Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase

Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase

Differential cytokine induction by doses of lipopolysaccharide and monophosphoryl lipid A that result in equivalent early endotoxin tolerance

Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of glucokinase gene expression in cultured rat hepatocytes: Regulation of gene transcription and messenger RNA degradation

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