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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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Dynamic insulin sensitivity as assessed from the OGTT (OGIS) in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in relative 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 = 0.049 CON before versus after; **P = 0.012 REL before versus after; † P = 0.009 RESP before versus after; ‡ P = 0.012 CON versus REL before; § P = 0.003, CON versus RESP before; $P = 0.031 CON versus RESP after exercise.
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Figure 2: Dynamic insulin sensitivity as assessed from the OGTT (OGIS) in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in relative 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 = 0.049 CON before versus after; **P = 0.012 REL before versus after; † P = 0.009 RESP before versus after; ‡ P = 0.012 CON versus REL before; § P = 0.003, CON versus RESP before; $P = 0.031 CON versus RESP after exercise.

Mentions: Fasting plasma glucose did not differ between groups (Table 3). The 2-h plasma glucose after oral glucose loading was within the normal range, slightly higher in relatives than in control subjects before (6.3 ± 1.4 vs. 5.0 ± 1.1 mmol/l, P = 0.009) but not after exercise (4.8 ± 1.2 vs. 5.5 ± 1.2 mmol/l). Plasma FFAs were comparable at baseline but were higher in relatives after training (P = 0.019). C-peptide was higher in relatives before (P = 0.006) and after exercise training (P = 0.031). Fasting plasma insulin tended to be increased in relatives. In subgroups, plasma RBP-4 (before training: control subjects 0.36 ± 0.12 and relatives 0.41 ± 0.07 ng/ml; after training: 0.36 ± 0.08 and 0.43 ± 0.09 ng/ml) and visfatin (before training: control subjects 39 ± 26 and relatives 29 ± 9 ng/ml; after training: 35 ± 13 and 26 ± 6 ng/ml) did not differ. At baseline, OGIS was 13% lower (P = 0.012) in relatives than in control subjects and rose slightly in both control subjects by 7% (P = 0.05) and in relatives by 12% (P = 0.012) after training (Fig. 2). The quantitative insulin-sensitivity check and insulinogenic indexes were comparable before and after training in both groups (Table 3).


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)

Dynamic insulin sensitivity as assessed from the OGTT (OGIS) in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in relative 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 = 0.049 CON before versus after; **P = 0.012 REL before versus after; † P = 0.009 RESP before versus after; ‡ P = 0.012 CON versus REL before; § P = 0.003, CON versus RESP before; $P = 0.031 CON versus RESP after exercise.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2682667&req=5

Figure 2: Dynamic insulin sensitivity as assessed from the OGTT (OGIS) in individuals without (CON, n = 12) or with (REL, n = 24) first-degree relatives with type 2 diabetes and in relative 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 = 0.049 CON before versus after; **P = 0.012 REL before versus after; † P = 0.009 RESP before versus after; ‡ P = 0.012 CON versus REL before; § P = 0.003, CON versus RESP before; $P = 0.031 CON versus RESP after exercise.
Mentions: Fasting plasma glucose did not differ between groups (Table 3). The 2-h plasma glucose after oral glucose loading was within the normal range, slightly higher in relatives than in control subjects before (6.3 ± 1.4 vs. 5.0 ± 1.1 mmol/l, P = 0.009) but not after exercise (4.8 ± 1.2 vs. 5.5 ± 1.2 mmol/l). Plasma FFAs were comparable at baseline but were higher in relatives after training (P = 0.019). C-peptide was higher in relatives before (P = 0.006) and after exercise training (P = 0.031). Fasting plasma insulin tended to be increased in relatives. In subgroups, plasma RBP-4 (before training: control subjects 0.36 ± 0.12 and relatives 0.41 ± 0.07 ng/ml; after training: 0.36 ± 0.08 and 0.43 ± 0.09 ng/ml) and visfatin (before training: control subjects 39 ± 26 and relatives 29 ± 9 ng/ml; after training: 35 ± 13 and 26 ± 6 ng/ml) did not differ. At baseline, OGIS was 13% lower (P = 0.012) in relatives than in control subjects and rose slightly in both control subjects by 7% (P = 0.05) and in relatives by 12% (P = 0.012) after training (Fig. 2). The quantitative insulin-sensitivity check and insulinogenic indexes were comparable before and after training in both groups (Table 3).

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