Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via AMP-Activated Protein Kinase
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Résumé
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.
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La notice
- Revue
- Diabetes
- Thématique
- Metabolism, Diabetes, and Cancer
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- —
- Organismes subventionnaires
- Australian Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchNational Health and Medical Research CouncilUniverza v LjubljaniJavna Agencija za Raziskovalno Dejavnost RSNational Research FoundationSundhed og Sygdom, Det Frie ForskningsrådDanmarks GrundforskningsfondCanadian Diabetes AssociationHeart and Stroke Foundation of Canada
- Mots-clés
- Glucose uptakeGLUT4Internal medicineAMPKEndocrinologyInsulinGlucose transporterCarbohydrate metabolismInsulin resistanceBeta oxidationProtein kinase AAMP-activated protein kinaseGlucose clamp techniqueBiologyFatty acidMetabolismChemistryKinaseBiochemistryPancreatic hormoneMedicine
- Résumé présent dans OpenAlex
- oui