Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin

J. Fan, D. Char, A. J. Kolasa, W. Pan, S. R. Maitra, C. S. Patlak, Z. Spolarics, M. C. Gelato, C. H. Lang

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 ± 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and - 4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by ~45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume269
Issue number1 32-1
StatePublished - Jan 1 1995

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Insulin-Like Growth Factor I
Endotoxins
Lipopolysaccharides
Liver
Kupffer Cells
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Peptides
Cell Separation
Intravenous Injections
Half-Life
Gastrointestinal Tract
Pancreas
Hepatocytes
Spleen
Endothelial Cells
Pharmacokinetics
Perfusion
Kidney
Lung

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Fan, J. ; Char, D. ; Kolasa, A. J. ; Pan, W. ; Maitra, S. R. ; Patlak, C. S. ; Spolarics, Z. ; Gelato, M. C. ; Lang, C. H. / Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin. In: American Journal of Physiology - Endocrinology and Metabolism. 1995 ; Vol. 269, No. 1 32-1.
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abstract = "Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50{\%}. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 ± 3 ng/min. In contrast, hepatic IGF-I output was decreased 46{\%} by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and - 4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by ~45{\%}. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration.",
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Fan, J, Char, D, Kolasa, AJ, Pan, W, Maitra, SR, Patlak, CS, Spolarics, Z, Gelato, MC & Lang, CH 1995, 'Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin', American Journal of Physiology - Endocrinology and Metabolism, vol. 269, no. 1 32-1.

Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin. / Fan, J.; Char, D.; Kolasa, A. J.; Pan, W.; Maitra, S. R.; Patlak, C. S.; Spolarics, Z.; Gelato, M. C.; Lang, C. H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 269, No. 1 32-1, 01.01.1995.

Research output: Contribution to journalArticle

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T1 - Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin

AU - Fan, J.

AU - Char, D.

AU - Kolasa, A. J.

AU - Pan, W.

AU - Maitra, S. R.

AU - Patlak, C. S.

AU - Spolarics, Z.

AU - Gelato, M. C.

AU - Lang, C. H.

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Y1 - 1995/1/1

N2 - Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 ± 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and - 4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by ~45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration.

AB - Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 ± 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and - 4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by ~45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration.

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