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

Autor:	Pesta D; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Jelenik T; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany., Zaharia OP; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany., Bobrov P; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany., Görgens S; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Paul-Langerhaus-Group Integrative Physiology, German Diabetes Center, Düsseldorf, Germany., Bódis K; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Karusheva Y; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany., Krako Jakovljevic N; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Clinics for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Lalic NM; Paul-Langerhaus-Group Integrative Physiology, German Diabetes Center, Düsseldorf, Germany., Markgraf DF; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany., Burkart V; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany., Müssig K; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Knebel B; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany., Kotzka J; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany., Eckel J; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Paul-Langerhaus-Group Integrative Physiology, German Diabetes Center, Düsseldorf, Germany., Strassburger K; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany., Szendroedi J; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Roden M; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2021 Sep 24; Vol. 12, pp. 693683. Date of Electronic Publication: 2021 Sep 24 (Print Publication: 2021).
DOI:	10.3389/fendo.2021.693683
Abstrakt:	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. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01055093. The trial was retrospectively registered on 25 th of January 2010. Competing Interests: MR receives research support by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Federal Ministry of Health, serves as investigator of studies supported by Boehringer-Ingelheim Pharma, Nutriticia/Danone and Sanofi and has served as advisor/consultant for Bristol-Myers Squibb, Eli Lilly, Gilead, Intercept Pharma, Novo Nordisk, Novartis, Poxel, Prosciento, Sanofi, Servier and TARGET NASH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2021 Pesta, Jelenik, Zaharia, Bobrov, Görgens, Bódis, Karusheva, Krako Jakovljevic, Lalic, Markgraf, Burkart, Müssig, Knebel, Kotzka, Eckel, Strassburger, Szendroedi and Roden.)
Databáze:	MEDLINE
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