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- Kacerovsky-Bielesz, Gertrud, et al.
(författare)
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A Single Nucleotide Polymorphism Associates With the Response of Muscle ATP Synthesis to Long-Term Exercise Training in Relatives of Type 2 Diabetic Humans
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 35:2, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort. RESEARCH DESIGN AND METHODS-A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO2) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with H-1/P-31 magnetic resonance spectroscopy. RESULTS Endurance training increased power output and VO2 by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 +/- 90 vs. 389 +/- 40 mL.min.m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 +/- 2.3 to 11.9 +/- 2.4 mu mol.mL(-1).m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I. CONCLUSIONS-Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.
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| 2. |
- Kacerovsky-Bielesz, Gertrud, et al.
(författare)
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Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:6, s. 1333-1341
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations With gene polymorphisms. RESEARCH DESIGN AND METHODS-We studied 24 nono-bese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest, and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using H-1 and P-31 magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS-Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin Sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O-2 uptake and insulin sensitivity. CONCLUSIONS-The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. lit addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. Diabetes 58:1333-1341, 2009
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| 3. |
- Moser, Ewald, et al.
(författare)
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7-T MR-from research to clinical applications?
- 2012
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480. ; 25:5, s. 695-716
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Forskningsöversikt (refereegranskat)abstract
- Over 20?000 MR systems are currently installed worldwide and, although the majority operate at magnetic fields of 1.5?T and below (i.e. about 70%), experience with 3-T (in high-field clinical diagnostic imaging and research) and 7-T (research only) human MR scanners points to a future in functional and metabolic MR diagnostics. Complementary to previous studies, this review attempts to provide an overview of ultrahigh-field MR research with special emphasis on emerging clinical applications at 7?T. We provide a short summary of the technical development and the current status of installed MR systems. The advantages and challenges of ultrahigh-field MRI and MRS are discussed with special emphasis on radiofrequency inhomogeneity, relaxation times, signal-to-noise improvements, susceptibility effects, chemical shifts, specific absorption rate and other safety issues. In terms of applications, we focus on the topics most likely to gain significantly from 7-T MR, i.e. brain imaging and spectroscopy and musculoskeletal imaging, but also body imaging, which is particularly challenging. Examples are given to demonstrate the advantages of susceptibility-weighted imaging, time-of-flight MR angiography, high-resolution functional MRI, 1H and 31P MRSI in the human brain, sodium and functional imaging of cartilage and the first results (and artefacts) using an eight-channel body array, suggesting future areas of research that should be intensified in order to fully explore the potential of 7-T MR systems for use in clinical diagnosis. Copyright (C) 2011 John Wiley & Sons, Ltd.
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| 4. |
- Votinov, Mikhail, et al.
(författare)
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A Genetic Polymorphism of the Endogenous Opioid Dynorphin Modulates Monetary Reward Anticipation in the Corticostriatal Loop
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The dynorphin/κ-opioid receptor (KOP-R) system has been shown to play a role in different types of behavior regulation, including reward-related behavior and drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N = 71 prescreened healthy participants to investigate the effect of this polymorphism on cerebral activation in the limbic-corticostriatal loop during reward anticipation. Individuals with the HH genotype showed higher activation than those with the LL genotype in the medial orbitofrontal cortex (mOFC) when anticipating a possible monetary reward. In addition, the HH genotype showed stronger functional coupling (as assessed by effective connectivity analyses) of mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during reward anticipation. This hints at a larger sensitivity for upcoming rewards in individuals with the HH genotype, resulting in a higher motivation to attain these rewards. These findings provide first evidence in humans that the PDYN polymorphism modulates neural processes associated with the anticipation of rewards, which ultimately may help to explain differences between genotypes with respect to addiction and drug abuse.
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