Pesta 2021 Front Endocrinol (Lausanne)

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Pesta D, Jelenik T, Zaharia OP, Bobrov P, Görgens S, Bódis K, Karusheva Y, Krako Jakovljevic N, Lalic NM, Markgraf DF, Burkart V, Müssig K, Knebel B, Kotzka J, Eckel J, Strassburger K, Szendroedi J, Roden M (2021) NDUFB6 polymorphism is associated with physical activity-mediated metabolic changes in type 2 diabetes. https://doi.org/10.3389/fendo.2021.693683

» Front Endocrinol (Lausanne) 12:693683. PMID: 34659107 Open Access

Pesta Dominik, Tomas Jelenik, Zaharia Oana-Patricia, Bobrov Pavel, Goergens Sven, Bodis Klaman, Karusheva Yanislava, Krako Jakovljevic Nina, Lalic Nebojsa M, Markgraf Daniel F, Burkart Volker, Muessig Karsten, Knebel Birgit, Kotzka Joerg, Eckel Juergen, Strassburger Klaus, Szendroedi Julia, Roden Michael (2021) Front Endocrinol (Lausanne)

Abstract: The rs540467 SNP in the NDUFB6 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 (VO2AT) by spiroergometry and PA by questionnaires. Translational studies investigated insulin signaling and mitochondrial function in Ndufb6 siRNA-treated C2C12 myotubes, with electronic pulse stimulation (EPS) to simulate exercising. PA levels were 10 and 6%, VO2AT 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 NDUFB6 rs540467 SNP modifies PA-mediated changes in insulin sensitivity, body composition and liver fat estimates in type 2 diabetes. Silencing Ndufb6 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 NDUFB6 gene, which may contribute to modulating mitochondrial function. Keywords: Diabetes mellitus, Insulin sensitivity, Mitochondrial function, Physical activity, Single nucleotide polymorphism Bioblast editor: Plangger M O2k-Network Lab: DE Cologne Pesta D, RS Belgrade Lalic NM, DE Duesseldorf Roden M


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N  HRR: Oxygraph-2k