Differential role of glucocorticoids in mediating endotoxin-induced changes in IGF-I and IGFBP-1

Li, Yue Hua; Fan, Jie; Lang, Charles H.

doi:10.1152/ajpregu.1997.272.6.r1990

Cited by 33 publications

(46 citation statements)

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“…Furthermore, this glucocorticoid was able to prevent the decrease in renal IGF-I mRNA caused by LPS. These results contrast with others previously reported (Li et al 1997), in which the LPS-induced decrease in hepatic IGF-I gene expression and the increase in renal IGF-I gene expression were attenuated by pretreatment with the antiglucocorticoid RU-486. However, in this study, the antagonistic action of RU-486 was not effective enough, since it did not increase corticosterone levels in rats treated with LPS.…”

Section: Discussioncontrasting

confidence: 99%

“…In fact, with doses of LPS lower than those used in the present study (Priego et al 2003a) or in arthritic rats (López-Calderón et al 2001) we found a decrease in hepatic IGF-I mRNA without changes in the GH receptor. Li et al (1997) reported that LPS increased renal IGF-I mRNA. Discrepancies with our findings could be due to liver and kidney IGF-I mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…Although the liver is the main source of serum IGF-I (Sjogren et al 1999), the kidney has also been reported as another source (Li et al 1997, Ibáñez de Cáceres et al 2002b. For this reason, hepatic and renal IGF-I and IGFBP-3 mRNA levels were measured.…”

Section: Introductionmentioning

confidence: 99%

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Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

Priego

Granado²,

Martín³

et al. 2005

Journal of Endocrinology

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The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein.Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPSinduced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

Priego

Granado²,

Martín³

et al. 2005

Journal of Endocrinology

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“…RU486 has a high affinity for cytosolic type II glucocorticoid receptors in various target tissues and exhibits little agonist activity (40). The dose of RU486 used in the present study has been shown to attenuate glucocorticoid-induced increases in catabolism and ameliorate endotoxin-or cytokine-induced changes in the IGF system and muscle protein balance (14,39,60).…”

Section: Methodsmentioning

confidence: 90%

“…The catabolic insults of LPS and sepsis produce a rapid and sustained elevation in the circulating concentration of glucocorticoids (13,39), and glucocorticoids have been generally reported to reduce IGFBP-5 mRNA under in vitro conditions (8,49). To examine the role of glucocorticoids, initial in vitro studies were performed by treating C 2 C 12 myocytes with dexamethasone.…”

Section: Lps-and Sepsis-induced Changes In Gastrocnemius Igfbp-5mentioning

confidence: 99%

Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism

Lang¹,

Krawiec²,

Huber³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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The purpose of the present study was to determine whether catabolic stimuli that induce muscle atrophy alter the muscle mRNA abundance of insulin-like growth factor binding protein (IGFBP)-4 and -5, and if so determine the physiological mechanism for such a change. Catabolic insults produced by endotoxin (LPS) and sepsis decreased IGFBP-5 mRNA time- and dose-dependently in gastrocnemius muscle. This reduction did not result from muscle disuse because hindlimb immobilization increased IGFBP-5. Continuous infusion of a nonlethal dose of tumor necrosis factor-α (TNF-α) decreased IGFBP-5 mRNA 70%, whereas pretreatment of septic rats with a neutralizing TNF binding protein completely prevented the reduction in muscle IGFBP-5. The addition of LPS or TNF-α to cultured C2C12 myoblasts also decreased IGFBP-5 expression. Although exogenously administered growth hormone (GH) increased IGFBP-5 mRNA 2-fold in muscle from control rats, muscle from septic animals was GH resistant and no such elevation was detected. In contrast, exogenous administration of IGF-I as part of a binary complex composed of IGF-I/IGFBP-3 produced comparable increases in IGFBP-5 mRNA in both control and septic muscle. Concomitant determinations of IGF-I mRNA content revealed a positive linear relationship between IGF-I and IGFBP-5 mRNA in the same muscle in response to LPS, sepsis, TNF-α, and GH treatment. Although dexamethasone decreased muscle IGFBP-5, pretreatment of rats with the glucocorticoid receptor antagonist RU486 did not prevent the sepsis-induced decrease in IGFBP-5 mRNA. In contrast, muscle IGFBP-4 mRNA abundance was not significantly altered by LPS, sepsis, or hindlimb immobilization. In summary, these data demonstrate that various inflammatory insults decrease muscle IGFBP-5 mRNA, without altering IGFBP-4, by a TNF-dependent glucocorticoid-independent mechanism. Finally, IGF-I appears to be a dominant positive regulator of IGFBP-5 gene expression in muscle under both normal and catabolic conditions.

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Endotoxin disrupts the leucine‐signaling pathway involving phosphorylation of mTOR, 4E‐BP1, and S6K1 in skeletal muscle

Lang

Frost

2004

Journal Cellular Physiology

112

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Endotoxin (i.e., lipopolysaccharide, LPS) impairs skeletal muscle protein synthesis. Although this impairment is not acutely associated with a decreased plasma concentration of total amino acids, LPS may blunt the anabolic response to amino acids. To examine this hypothesis, rats were injected intraperitoneally with LPS or saline (Sal) and 4 h thereafter were orally administered either leucine (Leu) or Sal. The gastrocnemius was removed 20 min later to assess signaling components important in the translational control of protein synthesis. In the Sal-Leu group phosphorylation of 4E-BP1 in muscle was markedly increased, compared to values from time-matched saline-treated control rats. This change was associated with a redistribution of eukaryotic initiation factor (eIF) 4E from the inactive eIF4E x 4E-BP1 complex to the active eIF4E x eIF4G complex. In LPS-treated rats, the Leu-induced phosphorylation of 4E-BP1 and changes in eIF4E distribution were partially or completely abrogated. LPS also antagonized the Leu-induced increase in phosphorylation of S6K1, ribosomal protein S6 and mTOR. Neither LPS nor leu altered the total amount or phosphorylation of TSC2 in muscle. The ability of LPS to blunt the anabolic effects of Leu could not be attributed to differences in the plasma concentrations of insulin or Leu between groups. Furthermore, the replacement of plasma insulin-like growth factor (IGF)-I in LPS-treated rats to basal levels also did not ameliorate the defect in leucine-induced phosphorylation of S6K1 or S6, although it did reverse the LPS-induced decrease in the constitutive phosphorylation of mTOR, S6 and 4E-BP1. Pretreatment with the glucocorticoid receptor antagonist RU486 was unable to prevent the LPS-induced leucine resistance. In contrast, to the abovementioned results with leucine, LPS did not prevent the ability of pharmacological levels of IGF-I to phosphorylate 4E-BP1, S6K1, mTOR or alter the availability of eIF4E. Hence, LPS working via a glucocorticoid-independent mechanism produces a leucine resistance in skeletal muscle that might be expected to impair the ability of this amino acid to stimulate translation initiation and protein synthesis.

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Differential role of glucocorticoids in mediating endotoxin-induced changes in IGF-I and IGFBP-1

Cited by 33 publications

References 0 publications

Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism

Endotoxin disrupts the leucine‐signaling pathway involving phosphorylation of mTOR, 4E‐BP1, and S6K1 in skeletal muscle

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