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- Title
Direct Effects of TNF-α on Local Fuel Metabolism and Cytokine Levels in the Placebo-Controlled, Bilaterally Infused Human Leg.
- Authors
Bach, Ermina; Nielsen, Roni R.; Vendelbo, Mikkel H.; Møller, Andreas B.; Jessen, Niels; Buhl, Mads; Hafstrøm, Thomas K.; Holm, Lars; Pedersen, Steen B.; Pilegaard, Henriette; Biensø, Rasmus S.; Jørgensen, Jens O. L.; Møller, Niels
- 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 6 0.17 vs. 0.74 6 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.
- Subjects
TUMOR necrosis factors; CYTOKINES; INTERLEUKIN-6; DIABETES complications; HYPERINSULINISM
- Publication
Diabetes, 2013, Vol 62, Issue 12, p4023
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db13-0138