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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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Skeletal muscle fATPase in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in REL subgroups responding (RESP, n = 10) or not responding (NRES, n = 14) with increased ATP synthesis after exercise training sessions. Black horizontal bars indicate mean values of the respective groups. *P < 0.001 CON and NRES before versus after; **P = 0.002, CON versus REL after; † P = 0.010 CON versus RESP before; $P = 0.009 RESP before versus after; § P = 0.024 RESP versus NRES before; ‡ P < 0.001 CON versus NRES after exercise.
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Figure 3: Skeletal muscle fATPase in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in REL subgroups responding (RESP, n = 10) or not responding (NRES, n = 14) with increased ATP synthesis after exercise training sessions. Black horizontal bars indicate mean values of the respective groups. *P < 0.001 CON and NRES before versus after; **P = 0.002, CON versus REL after; † P = 0.010 CON versus RESP before; $P = 0.009 RESP before versus after; § P = 0.024 RESP versus NRES before; ‡ P < 0.001 CON versus NRES after exercise.

Mentions: Baseline fATPase did not differ between groups (control subjects 12.0 ± 2.2 vs. relatives 11.1 ± 2.9 μmol · ml−1· muscle−1 · min−1) (Fig. 3). After training, fATPase increased by ∼18% (P = 0.0001) only in control subjects (14.2 ± 2.5 μmol · ml−1· muscle−1 · min−1) and was ∼23% (P = 0.002) higher than in relatives (10.9 ± 3.0 μmol · ml−1 · muscle−1 · min−1), in whom it did not change upon exercise training (Fig. 3). Similarly, k1rose in control subjects (P = 0.001) but not in relatives (P = 0.7). HCLs tended to be higher in relatives before training (control subjects 1.5 ± 1.0 vs. relatives 5.8 ± 7.5%, P = 0.08) (Fig. 4) but were not different after training (control subjects 1.8 ± 1.0 vs. relatives 4.4 ± 5.4%). IMCLs (Fig. 4) and G6P (data not shown) were not different between groups or affected by training.


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)

Skeletal muscle fATPase in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in REL subgroups responding (RESP, n = 10) or not responding (NRES, n = 14) with increased ATP synthesis after exercise training sessions. Black horizontal bars indicate mean values of the respective groups. *P < 0.001 CON and NRES before versus after; **P = 0.002, CON versus REL after; † P = 0.010 CON versus RESP before; $P = 0.009 RESP before versus after; § P = 0.024 RESP versus NRES before; ‡ P < 0.001 CON versus NRES after exercise.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2682667&req=5

Figure 3: Skeletal muscle fATPase in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in REL subgroups responding (RESP, n = 10) or not responding (NRES, n = 14) with increased ATP synthesis after exercise training sessions. Black horizontal bars indicate mean values of the respective groups. *P < 0.001 CON and NRES before versus after; **P = 0.002, CON versus REL after; † P = 0.010 CON versus RESP before; $P = 0.009 RESP before versus after; § P = 0.024 RESP versus NRES before; ‡ P < 0.001 CON versus NRES after exercise.
Mentions: Baseline fATPase did not differ between groups (control subjects 12.0 ± 2.2 vs. relatives 11.1 ± 2.9 μmol · ml−1· muscle−1 · min−1) (Fig. 3). After training, fATPase increased by ∼18% (P = 0.0001) only in control subjects (14.2 ± 2.5 μmol · ml−1· muscle−1 · min−1) and was ∼23% (P = 0.002) higher than in relatives (10.9 ± 3.0 μmol · ml−1 · muscle−1 · min−1), in whom it did not change upon exercise training (Fig. 3). Similarly, k1rose in control subjects (P = 0.001) but not in relatives (P = 0.7). HCLs tended to be higher in relatives before training (control subjects 1.5 ± 1.0 vs. relatives 5.8 ± 7.5%, P = 0.08) (Fig. 4) but were not different after training (control subjects 1.8 ± 1.0 vs. relatives 4.4 ± 5.4%). IMCLs (Fig. 4) and G6P (data not shown) were not different between groups or affected by training.

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