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
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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, 2013, p. 4023-4029.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo controlled bilaterally infused human leg
T2 - 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
Y1 - 2013
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 - Journal article
C2 - 23835341
VL - 62
SP - 4023
EP - 4029
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 12
ER -
ID: 47452669