Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release

Research output: Contribution to journalArticlepeer-review

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Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. / Bach, E.; Nielsen, Roni R.; Vendelbo, M; Møller, Andreas Buch; Jessen, N; Buhl, M; Hafstrøm, Thomas Krusenstjerna-; Holm, Lars; Pedersen, Steen Bønløkke; Pilegaard, H; Biensøe, Rasmus S; Jørgensen, Jens O L; Møller, N.

In: Diabetes, Vol. 62, No. 12, 12.2013, p. 4023-4029.

Research output: Contribution to journalArticlepeer-review

Harvard

Bach, E, Nielsen, RR, Vendelbo, M, Møller, AB, Jessen, N, Buhl, M, Hafstrøm, TK, Holm, L, Pedersen, SB, Pilegaard, H, Biensøe, RS, Jørgensen, JOL & Møller, N 2013, 'Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release', Diabetes, vol. 62, no. 12, pp. 4023-4029. https://doi.org/10.2337/db13-0138

APA

Bach, E., Nielsen, R. R., Vendelbo, M., Møller, A. B., Jessen, N., Buhl, M., Hafstrøm, T. K., Holm, L., Pedersen, S. B., Pilegaard, H., Biensøe, R. S., Jørgensen, J. O. L., & Møller, N. (2013). Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. Diabetes, 62(12), 4023-4029. https://doi.org/10.2337/db13-0138

Vancouver

Author

Bach, E. ; Nielsen, Roni R. ; Vendelbo, M ; Møller, Andreas Buch ; Jessen, N ; Buhl, M ; Hafstrøm, Thomas Krusenstjerna- ; Holm, Lars ; Pedersen, Steen Bønløkke ; Pilegaard, H ; Biensøe, Rasmus S ; Jørgensen, Jens O L ; Møller, N. / Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. In: Diabetes. 2013 ; Vol. 62, No. 12. pp. 4023-4029.

Bibtex

@article{f440a58a145844bd9ed9428816238f3d,
title = "Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release",
abstract = "Tumor necrosis factor-α (TNF-α) has widespread metabolic actions. Systemic TNF-α administration, however, generates a complex hormonal and metabolic response. Our study was designed to test whether regional, placebo-controlled TNF-α infusion directly affects insulin resistance and protein breakdown. We studied eight healthy volunteers once with bilateral femoral vein and artery catheters during a 3-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. One artery was perfused with saline and one with TNF-α. During the clamp, TNF-α perfusion increased glucose arteriovenous differences (0.91 ± 0.17 vs. 0.74 ± 0.15 mmol/L, P = 0.012) and leg glucose uptake rates. Net phenylalanine release was increased by TNF-α perfusion with concomitant increases in appearance and disappearance rates. Free fatty acid kinetics was not affected by TNF-α, whereas interleukin-6 (IL-6) release increased. Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical interest and may concurrently act to provide adequate tissue fuel supply and contribute to the occurrence of systemic hypoglycemia. This distinct metabolic feature places TNF-α among the rare insulin mimetics of human origin.",
author = "E. Bach and Nielsen, {Roni R.} and M Vendelbo and M{\o}ller, {Andreas Buch} and N Jessen and M Buhl and Hafstr{\o}m, {Thomas Krusenstjerna-} and Lars Holm and Pedersen, {Steen B{\o}nl{\o}kke} and H Pilegaard and Biens{\o}e, {Rasmus S} and J{\o}rgensen, {Jens O L} and N M{\o}ller",
year = "2013",
month = dec,
doi = "10.2337/db13-0138",
language = "English",
volume = "62",
pages = "4023--4029",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "12",

}

RIS

TY - JOUR

T1 - Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release

AU - Bach, E.

AU - Nielsen, Roni R.

AU - Vendelbo, M

AU - Møller, Andreas Buch

AU - Jessen, N

AU - Buhl, M

AU - Hafstrøm, Thomas Krusenstjerna-

AU - Holm, Lars

AU - Pedersen, Steen Bønløkke

AU - Pilegaard, H

AU - Biensøe, Rasmus S

AU - Jørgensen, Jens O L

AU - Møller, N

PY - 2013/12

Y1 - 2013/12

N2 - Tumor necrosis factor-α (TNF-α) has widespread metabolic actions. Systemic TNF-α administration, however, generates a complex hormonal and metabolic response. Our study was designed to test whether regional, placebo-controlled TNF-α infusion directly affects insulin resistance and protein breakdown. We studied eight healthy volunteers once with bilateral femoral vein and artery catheters during a 3-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. One artery was perfused with saline and one with TNF-α. During the clamp, TNF-α perfusion increased glucose arteriovenous differences (0.91 ± 0.17 vs. 0.74 ± 0.15 mmol/L, P = 0.012) and leg glucose uptake rates. Net phenylalanine release was increased by TNF-α perfusion with concomitant increases in appearance and disappearance rates. Free fatty acid kinetics was not affected by TNF-α, whereas interleukin-6 (IL-6) release increased. Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical interest and may concurrently act to provide adequate tissue fuel supply and contribute to the occurrence of systemic hypoglycemia. This distinct metabolic feature places TNF-α among the rare insulin mimetics of human origin.

AB - Tumor necrosis factor-α (TNF-α) has widespread metabolic actions. Systemic TNF-α administration, however, generates a complex hormonal and metabolic response. Our study was designed to test whether regional, placebo-controlled TNF-α infusion directly affects insulin resistance and protein breakdown. We studied eight healthy volunteers once with bilateral femoral vein and artery catheters during a 3-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. One artery was perfused with saline and one with TNF-α. During the clamp, TNF-α perfusion increased glucose arteriovenous differences (0.91 ± 0.17 vs. 0.74 ± 0.15 mmol/L, P = 0.012) and leg glucose uptake rates. Net phenylalanine release was increased by TNF-α perfusion with concomitant increases in appearance and disappearance rates. Free fatty acid kinetics was not affected by TNF-α, whereas interleukin-6 (IL-6) release increased. Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical interest and may concurrently act to provide adequate tissue fuel supply and contribute to the occurrence of systemic hypoglycemia. This distinct metabolic feature places TNF-α among the rare insulin mimetics of human origin.

U2 - 10.2337/db13-0138

DO - 10.2337/db13-0138

M3 - Article

VL - 62

SP - 4023

EP - 4029

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -