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Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.

Kacerovsky-Bielesz G, Chmelik M, Ling C, Pokan R, Szendroedi J, Farukuoye M, Kacerovsky M, Schmid AI, Gruber S, Wolzt M, Moser E, Pacini G, Smekal G, Groop L, Roden M - Diabetes (2009)

Bottom Line: In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using(1)H and(31)P magnetic resonance spectroscopy, respectively.They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467).In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation.

View Article: PubMed Central - PubMed

Affiliation: Medical Department, Hanusch Hospital, Vienna, Austria.

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 nonobese 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(1)H and(31)P 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. In 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.

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Related in: MedlinePlus

31P magnetic resonance spectrum acquired at 3-T using a surface coil (repetition time = 15 s, number of scans = 16) positioned under the calf muscle of one participant. The spectrum shows intramyocellular phosphomonoesters (PME) including G6P, Pi, PDEs, phosphocreatine (PCr), and ATP. Inset: 31P spectra with saturation of γ-ATP (bottom) and with saturation mirrored around Pi (top), which was always used to account and correct for direct saturation of the resonance frequency pulse.
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Figure 1: 31P magnetic resonance spectrum acquired at 3-T using a surface coil (repetition time = 15 s, number of scans = 16) positioned under the calf muscle of one participant. The spectrum shows intramyocellular phosphomonoesters (PME) including G6P, Pi, PDEs, phosphocreatine (PCr), and ATP. Inset: 31P spectra with saturation of γ-ATP (bottom) and with saturation mirrored around Pi (top), which was always used to account and correct for direct saturation of the resonance frequency pulse.

Mentions: Participants were studied in a 3-T magnetic resonance spectrometer (Bruker, Bremen, Germany). A 10-cm circular double resonant1H/31P surface coil was used for quantifying HCLs and phosphorus metabolites. A 28-cm birdcage coil was positioned over the right lower leg for measuring IMCLs in soleus and tibialis anterior muscles. For nonlocalized31P MRS, the right calf was positioned on the surface coil with the medial head of the right gastrocnemius muscle in the coil center. The integrals of the region of phosphomonoesters covering G6P (7.1–7.4 ppm), phosphodiesters (PDEs), Pi, and phosphocreatine were measured from the ratio of integrated peak intensities and β-ATP resonance intensity in spectra without inversion and saturation, assuming an ATP concentration of 5.5 mmol/l (Fig. 1). The assumption of constant ATP before and after exercise training was supported by unchanged ATP/PDE ratios (data not shown), because PDE levels remain constant under similar conditions (22). Absolute quantification would be required to detect subtle changes of myocellular ATP concentrations, which do not necessarily reflect actual fATPase. The saturation transfer experiment (selective irradiation of γ-ATP) was used to measure the exchange rate (k1) between Pi and ATP and to calculate fATPase from k1 × [Pi ] (5,8) (Fig. 1). IMCLs and HCLs were determined within volumes of interest of 1.73 cm3(23) and 27 cm3(5), respectively.


Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.

Kacerovsky-Bielesz G, Chmelik M, Ling C, Pokan R, Szendroedi J, Farukuoye M, Kacerovsky M, Schmid AI, Gruber S, Wolzt M, Moser E, Pacini G, Smekal G, Groop L, Roden M - Diabetes (2009)

31P magnetic resonance spectrum acquired at 3-T using a surface coil (repetition time = 15 s, number of scans = 16) positioned under the calf muscle of one participant. The spectrum shows intramyocellular phosphomonoesters (PME) including G6P, Pi, PDEs, phosphocreatine (PCr), and ATP. Inset: 31P spectra with saturation of γ-ATP (bottom) and with saturation mirrored around Pi (top), which was always used to account and correct for direct saturation of the resonance frequency pulse.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682667&req=5

Figure 1: 31P magnetic resonance spectrum acquired at 3-T using a surface coil (repetition time = 15 s, number of scans = 16) positioned under the calf muscle of one participant. The spectrum shows intramyocellular phosphomonoesters (PME) including G6P, Pi, PDEs, phosphocreatine (PCr), and ATP. Inset: 31P spectra with saturation of γ-ATP (bottom) and with saturation mirrored around Pi (top), which was always used to account and correct for direct saturation of the resonance frequency pulse.
Mentions: Participants were studied in a 3-T magnetic resonance spectrometer (Bruker, Bremen, Germany). A 10-cm circular double resonant1H/31P surface coil was used for quantifying HCLs and phosphorus metabolites. A 28-cm birdcage coil was positioned over the right lower leg for measuring IMCLs in soleus and tibialis anterior muscles. For nonlocalized31P MRS, the right calf was positioned on the surface coil with the medial head of the right gastrocnemius muscle in the coil center. The integrals of the region of phosphomonoesters covering G6P (7.1–7.4 ppm), phosphodiesters (PDEs), Pi, and phosphocreatine were measured from the ratio of integrated peak intensities and β-ATP resonance intensity in spectra without inversion and saturation, assuming an ATP concentration of 5.5 mmol/l (Fig. 1). The assumption of constant ATP before and after exercise training was supported by unchanged ATP/PDE ratios (data not shown), because PDE levels remain constant under similar conditions (22). Absolute quantification would be required to detect subtle changes of myocellular ATP concentrations, which do not necessarily reflect actual fATPase. The saturation transfer experiment (selective irradiation of γ-ATP) was used to measure the exchange rate (k1) between Pi and ATP and to calculate fATPase from k1 × [Pi ] (5,8) (Fig. 1). IMCLs and HCLs were determined within volumes of interest of 1.73 cm3(23) and 27 cm3(5), respectively.

Bottom Line: In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using(1)H and(31)P magnetic resonance spectroscopy, respectively.They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467).In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation.

View Article: PubMed Central - PubMed

Affiliation: Medical Department, Hanusch Hospital, Vienna, Austria.

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 nonobese 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(1)H and(31)P 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. In 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.

Show MeSH
Related in: MedlinePlus