Abstract
Although interleukin-6 (IL-6) has been associated with insulin resistance, little is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo. Here, we show that IL-6 infusion increases glucose disposal without affecting the complete suppression of endogenous glucose production during a hyperinsulinemic-euglycemic clamp in healthy humans. Because skeletal muscle accounts for most of the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by which IL-6 may affect muscle metabolism using L6 myotubes. IL-6 treatment increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increased AMP-activated protein kinase (AMPK). To determine whether the activation of AMPK mediated cellular metabolic events, we conducted experiments using L6 myotubes infected with dominant-negative AMPK alpha-subunit. The effects described above were abrogated in AMPK dominant-negative-infected cells. Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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AMP-Activated Protein Kinases
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Adult
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Cell Line
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Cell Membrane / metabolism
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Fatty Acids / metabolism*
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Glucose / metabolism*
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Glucose Clamp Technique
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Glucose Transporter Type 4
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Humans
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Hyperinsulinism / physiopathology
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Insulin / physiology*
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Interleukin-6 / pharmacology*
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Interleukin-6 / physiology
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Male
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Mice
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Mice, Knockout
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Multienzyme Complexes / metabolism*
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Myoblasts
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Protein Serine-Threonine Kinases / metabolism*
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Rats
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Recombinant Proteins / pharmacology
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Ribonucleotides / pharmacology
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / metabolism
Substances
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Fatty Acids
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Glucose Transporter Type 4
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Insulin
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Interleukin-6
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Multienzyme Complexes
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Recombinant Proteins
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Ribonucleotides
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STAT3 Transcription Factor
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Slc2a4 protein, rat
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Socs3 protein, rat
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Stat3 protein, rat
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Aminoimidazole Carboxamide
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Protein Serine-Threonine Kinases
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AMP-Activated Protein Kinases
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AICA ribonucleotide
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Glucose