Universität zu Köln

Pesta, Dominik, Jelenik, Tomas, Zaharia, Oana-Patricia, Bobrov, Pavel, Gorgens, Sven, Bodis, Kalman, Karusheva, Yanislava, Jakovljevic, Nina Krako, Lalic, Nebojsa M., Markgraf, Daniel F., Burkart, Volker, Mussig, Karsten, Knebel, Birgit, Kotzka, Jorg, Eckel, Jurgen, Strassburger, Klaus, Szendroedi, Julia and Roden, Michael (2021). NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes. Front. Endocrinol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-2392

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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 (VO(2)AT) 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%, VO(2)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 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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pesta, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Jelenik, Tomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaharia, Oana-Patricia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bobrov, Pavel UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorgens, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Bodis, Kalman UNSPECIFIED UNSPECIFIED UNSPECIFIED Karusheva, Yanislava UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakovljevic, Nina Krako UNSPECIFIED UNSPECIFIED UNSPECIFIED Lalic, Nebojsa M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Markgraf, Daniel F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burkart, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Mussig, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Knebel, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotzka, Jorg UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckel, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Strassburger, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Szendroedi, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Roden, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597072
DOI:	10.3389/fendo.2021.693683
Journal or Publication Title:	Front. Endocrinol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-2392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUSCLE ATP SYNTHESIS; INSULIN-RESISTANCE; WEIGHT-LOSS; MITOCHONDRIAL-FUNCTION; SKELETAL-MUSCLE; FAT-CONTENT; EXERCISE; GLUCOSE; PHOSPHORYLATION; QUESTIONNAIRES Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59707