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

Pesta, Dominik and Jelenik, Tomas and Zaharia, Oana-Patricia and Bobrov, Pavel and Görgens, Sven and Bódis, Kálmán and Karusheva, Yanislava and Krako Jakovljevic, Nina and Lalic, Nebojsa M. and Markgraf, Daniel F. and Burkart, Volker and Müssig, Karsten and Knebel, Birgit and Kotzka, Jörg and Eckel, Jürgen and Strassburger, Klaus and Szendroedi, Julia and Roden, Michael (2021) NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes. Frontiers in Endocrinology, 12, p. 693683. Frontiers Media S.A.. doi: 10.3389/fendo.2021.693683. ISSN 1664-2392.

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Official URL: http://dx.doi.org/10.3389/fendo.2021.693683

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.

Item URL in elib:https://elib.dlr.de/185544/
Document Type:Article
Title:NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Pesta, DominikInstitute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany; Dominik.Pesta (at) dlr.dehttps://orcid.org/0000-0002-5089-3586
Jelenik, TomasUNSPECIFIEDUNSPECIFIED
Zaharia, Oana-PatriciaUNSPECIFIEDUNSPECIFIED
Bobrov, PavelUNSPECIFIEDUNSPECIFIED
Görgens, SvenUNSPECIFIEDUNSPECIFIED
Bódis, KálmánUNSPECIFIEDUNSPECIFIED
Karusheva, YanislavaUNSPECIFIEDUNSPECIFIED
Krako Jakovljevic, NinaUNSPECIFIEDUNSPECIFIED
Lalic, Nebojsa M.UNSPECIFIEDUNSPECIFIED
Markgraf, Daniel F.UNSPECIFIEDUNSPECIFIED
Burkart, VolkerUNSPECIFIEDUNSPECIFIED
Müssig, KarstenUNSPECIFIEDUNSPECIFIED
Knebel, BirgitUNSPECIFIEDUNSPECIFIED
Kotzka, JörgUNSPECIFIEDUNSPECIFIED
Eckel, JürgenUNSPECIFIEDUNSPECIFIED
Strassburger, KlausUNSPECIFIEDUNSPECIFIED
Szendroedi, JuliaUNSPECIFIEDUNSPECIFIED
Roden, MichaelUNSPECIFIEDUNSPECIFIED
Date:24 September 2021
Journal or Publication Title:Frontiers in Endocrinology
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:12
DOI :10.3389/fendo.2021.693683
Page Range:p. 693683
Publisher:Frontiers Media S.A.
ISSN:1664-2392
Status:Published
Keywords:diabetes mellitus; insulin sensitivity; mitochondrial function; physical activity; single nucleotide polymorphism
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Muscle Mechanics and Metabolism
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine
Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Pesta, Dominik
Deposited On:08 Apr 2022 12:32
Last Modified:12 Apr 2022 13:02

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