PMID- 23835341
OWN - NLM
STAT- MEDLINE
DCOM- 20140117
LR  - 20211021
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 62
IP  - 12
DP  - 2013 Dec
TI  - Direct effects of TNF-alpha 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.
PG  - 4023-9
LID - 10.2337/db13-0138 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) has widespread metabolic actions. Systemic TNF-alpha 
      administration, however, generates a complex hormonal and metabolic response. Our 
      study was designed to test whether regional, placebo-controlled TNF-alpha 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-alpha. During the clamp, TNF-alpha 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-alpha perfusion with concomitant increases in appearance and disappearance 
      rates. Free fatty acid kinetics was not affected by TNF-alpha, whereas interleukin-6 
      (IL-6) release increased. Insulin and protein signaling in muscle biopsies was 
      not affected by TNF-alpha. TNF-alpha 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-alpha among the rare insulin mimetics of human origin.
FAU - Bach, Ermina
AU  - Bach E
AD  - Medical Research Laboratories, Institute for Clinical Medicine, Aarhus 
      University, Aarhus, Denmark.
FAU - Nielsen, Roni R
AU  - Nielsen RR
FAU - Vendelbo, Mikkel H
AU  - Vendelbo MH
FAU - Moller, Andreas B
AU  - Moller AB
FAU - Jessen, Niels
AU  - Jessen N
FAU - Buhl, Mads
AU  - Buhl M
FAU - K-Hafstrom, Thomas
AU  - K-Hafstrom T
FAU - Holm, Lars
AU  - Holm L
FAU - Pedersen, Steen B
AU  - Pedersen SB
FAU - Pilegaard, Henriette
AU  - Pilegaard H
FAU - Bienso, Rasmus S
AU  - Bienso RS
FAU - Jorgensen, Jens O L
AU  - Jorgensen JO
FAU - Moller, Niels
AU  - Moller N
LA  - eng
SI  - ClinicalTrials.gov/NCT01452958
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130708
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - Cytokines/*blood
MH  - Energy Metabolism/*drug effects
MH  - Femoral Artery/drug effects/metabolism
MH  - Glucose Clamp Technique
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Resistance/*physiology
MH  - Interleukin-6/*metabolism
MH  - Leg/blood supply
MH  - Male
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Single-Blind Method
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC3837036
EDAT- 2013/07/10 06:00
MHDA- 2014/01/18 06:00
PMCR- 2014/12/01
CRDT- 2013/07/10 06:00
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/01/18 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - db13-0138 [pii]
AID - 0138 [pii]
AID - 10.2337/db13-0138 [doi]
PST - ppublish
SO  - Diabetes. 2013 Dec;62(12):4023-9. doi: 10.2337/db13-0138. Epub 2013 Jul 8.