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. 2009 Jun;58(6):1333-41.
doi: 10.2337/db08-1240. Epub 2009 Mar 5.

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

Gertrud Kacerovsky-Bielesz  1 , Marek Chmelik, Charlotte Ling, Rochus Pokan, Julia Szendroedi, Michaela Farukuoye, Michaela Kacerovsky, Albrecht I Schmid, Stephan Gruber, Michael Wolzt, Ewald Moser, Giovanni Pacini, Gerhard Smekal, Leif Groop, Michael Roden
Affiliations

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

Gertrud Kacerovsky-Bielesz et al. Diabetes. 2009 Jun.

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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Figures

FIG. 1.
FIG. 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.
FIG. 2.
FIG. 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.
FIG. 3.
FIG. 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.
FIG. 4.
FIG. 4.
Absolute changes (Δ; means ± SE) in dynamic insulin sensitivity (OGIS) (A), fATPase (B), and lipid concentrations in liver (HCL) (C) and soleus muscle (IMCL) (D) 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. *P = 0.005 CON versus REL; **P < 0.001 RESP versus NRES; § P < 0.001 CON versus NRES; † P = 0.014 REL versus RESP; $P = 0.024 REL versus NRES.
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