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Pesta, Dominik; Jelenik, Tomas; Zaharia, Oana-Patricia; Bobrov, Pavel; Görgens, Sven; Bódis, Kálmán; Karusheva, Yanislava; Krako Jakovljevic, Nina; Lalic, Nebojsa M.; Markgraf, Daniel F.; Burkart, Volker; Müssig, Karsten; Knebel, Birgit; Kotzka, Jörg; Eckel, Jürgen; Strassburger, Klaus; Szendroedi, Julia; Roden, Michael

NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes

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  • Medientyp: E-Artikel
  • Titel: NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes
  • Beteiligte: Pesta, Dominik; Jelenik, Tomas; Zaharia, Oana-Patricia; Bobrov, Pavel; Görgens, Sven; Bódis, Kálmán; Karusheva, Yanislava; Krako Jakovljevic, Nina; Lalic, Nebojsa M.; Markgraf, Daniel F.; Burkart, Volker; Müssig, Karsten; Knebel, Birgit; Kotzka, Jörg; Eckel, Jürgen; Strassburger, Klaus; Szendroedi, Julia; Roden, Michael
  • Erschienen: Frontiers Media SA, 2021
  • Erschienen in: Frontiers in Endocrinology
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fendo.2021.693683
  • ISSN: 1664-2392
  • Schlagwörter: Endocrinology, Diabetes and Metabolism
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>The rs540467 SNP in the <jats:italic>NDUFB6</jats:italic> gene, encoding a mitochondrial complex I subunit, has been shown to modulate adaptations to exercise training. Interaction effects with diabetes mellitus remain unclear. We assessed associations of habitual physical activity (PA) levels with metabolic variables and examined a possible modifying effect of the rs540467 SNP. Volunteers with type 2 (n=242), type 1 diabetes (n=250) or normal glucose tolerance (control; n=139) were studied at diagnosis and subgroups with type 1 (n=96) and type 2 diabetes (n=95) after 5 years. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, oxygen uptake at the ventilator threshold (VO<jats:sub>2</jats:sub>AT) by spiroergometry and PA by questionnaires. Translational studies investigated insulin signaling and mitochondrial function in <jats:italic>Ndufb6</jats:italic> siRNA-treated C2C12 myotubes, with electronic pulse stimulation (EPS) to simulate exercising. PA levels were 10 and 6%, VO<jats:sub>2</jats:sub>AT was 31% and 8% lower in type 2 and type 1 diabetes compared to control. Within 5 years, 36% of people with type 2 diabetes did not improve their insulin sensitivity despite increasing PA levels. The <jats:italic>NDUFB6</jats:italic> rs540467 SNP modifies PA-mediated changes in insulin sensitivity, body composition and liver fat estimates in type 2 diabetes. Silencing <jats:italic>Ndufb6</jats:italic> in myotubes reduced mitochondrial respiration and prevented rescue from palmitate-induced insulin resistance after EPS. A substantial proportion of humans with type 2 diabetes fails to respond to rising PA with increasing insulin sensitivity. This may at least partly relate to a polymorphism of the <jats:italic>NDUFB6</jats:italic> gene, which may contribute to modulating mitochondrial function.</jats:p><jats:sec><jats:title>Clinical Trial Registration</jats:title><jats:p>ClinicalTrials.gov, identifier NCT01055093. The trial was retrospectively registered on 25<jats:sup>th</jats:sup> of January 2010.</jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang