The Effect of Insulin-like Growth Factor-1 on Protein Metabolism and Hepatic Response to Endotoxemia in Parenterally Fed Rats

Dickerson, Roland N.; Manzo, Claudia; Charland, Scott L.; Settle, R. Gregg; Stein, T. Peter; Kuhl, David A.; Rajter, Jean-Jacques

doi:10.1006/jsre.1995.1041

Cited by 21 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, twice daily injections of IGF-I/IGFBP-3 binary complex partially restores protein content in gastrocnemius through a restoration of rates of protein synthesis (43). These observations are in contrast with those in liver (8,43), where elevations in plasma IGF-I did not modulate hepatic protein synthesis, yet improved cumulative nitrogen balance compared with untreated septic rats. Thus protein synthesis in gastrocnemius seems more responsive to IGF-I than other organs of the body during sepsis.…”

Section: Discussionmentioning

confidence: 71%

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

Vary¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Chronic septic abscess formation causes an inhibition of protein synthesis in gastrocnemius not observed in rats with a sterile abscess. Inhibition is associated with an impaired mRNA translation initiation that can be ameliorated by elevating IGF-I but not insulin. The present study investigated the ability of IGF-I signaling to stimulate protein synthesis in gastrocnemius by accelerating mRNA translation initiation. Experiments were performed in perfused hindlimb preparations from rats 5 days after induction of a septic abscess. Protein synthesis in gastrocnemius from septic rats was accelerated twofold by the addition of IGF-I (10 nM) to perfusate. IGF-I increased the phosphorylation of translation repressor 4E-binding protein-1 (4E-BP1). Hyperphosphorylation of 4E-BP1 in response to IGF-I resulted in its dissociation from the inactive eukaryotic initiation factor (eIF) 4E.4E-BP1 complex. Assembly of the active eIF4F complex (as assessed by the association eIF4G with eIF4E) was increased twofold by IGF-I in the perfusate. In addition, phosphorylation of eIF4G and ribosomal protein S6 kinase-1 (S6K1) was also enhanced by IGF-I. Activation of mammalian target of rapamycin, an upstream kinase implicated in phosphorylating both 4E-BP1 and S6K1, was also observed. Thus the ability of IGF-I to accelerate protein synthesis during sepsis may be related to a stimulation of signaling to multiple steps in translation initiation with an ensuing increased phosphorylation of eIF4G, eIF4E availability, and S6K1 phosphorylation.

show abstract

Section: Discussionmentioning

confidence: 71%

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

Vary¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…We did not study hemodynamic and liver blood flow effects of this intravenous live E. coli sepsis model; however, hypermetabolism and alterations in metabolism associated with sepsis were clearly evident by 48 hours in this model, as well as in other models of sepsis in rats. [14][15][16][17][30][31][32][33] Sex may influence CYP activity. Rats have substantial differences in a number of hepatic CYP isoenzyme activities between sexes, with males generally having greater CYP activity than females.…”

Section: Discussionmentioning

confidence: 99%

“…37 The etiology of reduction in hepatic oxidase function may be related to the presence of endotoxemia, as exogenous endotoxin administration reduces hepatic CYP content by 29-44% 4-6, 9, 14, 37-39 and various isoenzyme activities by as much as 22-72%. 5,6,9,14,23 In addition, these reductions may be related to various cytokine mediators that depress CYP activity, such as interleukin-1, 4, 7, 40 interleukin-6, 4, 8 interferon, 41 interleukin-2, 42 or tumor necrosis factor, 40,43 which are elicited during the acute host response to sepsis. It also was suggested that nitric oxide production may be the mediator for hepatic CYP dysfunction induced by endotoxin.…”

Section: Discussionmentioning

confidence: 99%

“…On the fourth day animals were anesthetized with ketamine 87 mg/kg-xylazine 13 mg/kg intraperitoneally, and a central venous cannula was placed through the right external jugular vein as described elsewhere. [14][15][16][17] Postoperatively, animals were maintained with nothing by mouth except for water ad libitum. Immediately after cannulation, the animals received an infusion of normal saline at 1.5 ml/hour through the central venous catheter to permit recovery from anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…18 The energy and protein intake provided by this regimen achieves positive nitrogen balance or nitrogen equilibrium in unstressed healthy rats. [14][15][16][17] The CH animals were offered chow ad libitum after the recovery period, and intravenous fluids were discontinued. Animals from each group were allowed water ad libitum for the entire study.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The Effect of Sepsis During Parenteral Nutrition on Hepatic Microsomal Function in Rats

Dickerson

Charland

2002

Pharmacotherapy

Self Cite

View full text Add to dashboard Cite

show abstract

Octreotide and Potassium Homeostasis

Brown,

Dickerson,

Mouser

et al. 1997

Pharmacotherapy

View full text Add to dashboard Cite

Somatostatin infusion causes hyperkalemia in healthy subjects and in some animal models. The purpose of this investigation was to determine what effect octreotide has on potassium homeostasis during serious illness and if there is a dose‐response relationship. Sixty‐six male Sprague‐Dawley rats (185–225 g) were randomized to receive parenteral nutrition (PN) only, PN plus continuous infusion of Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus octreotide 10, 100, or 1000 μg/kg/day for 48 hours. Before randomization all animals received isocaloric, isonitrogenous, isokalemic PN. A 24‐hour urine was collected and a blood sample was taken at the end of the study immediately before euthanization. Data were analyzed by ANOVA and Duncan's multiple range test. Nonhemolyzed serum samples from 50 rats were available for study. Serum potassium concentrations were in the normal range for rats and did not differ significantly among the groups: 5.97 ± 0.86, 5.96 ± 1.58, 5.78 ± 1.48, 5.79 ± 1.67, 5.35 ± 0.78 mEq/L, respectively. No differences among groups were found for fractional excretion of potassium or serum creatinine concentration. Octreotide administration in escalating dosages does not cause hyperkalemia in endotoxemic rats given intravenous potassium at a constant rate by PN.

show abstract

The Effect of Insulin-like Growth Factor-1 on Protein Metabolism and Hepatic Response to Endotoxemia in Parenterally Fed Rats

Cited by 21 publications

References 0 publications

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

The Effect of Sepsis During Parenteral Nutrition on Hepatic Microsomal Function in Rats

Octreotide and Potassium Homeostasis

Contact Info

Product

Resources

About