(07-08-12) Physical Activity Is the Key Determinant of Skeletal Muscle Mitochondrial Function in Type 2 Diabetes.

van Tienen FH, Praet SF, de Feyter HM, van den Broek NM, Lindsey PJ,
Schoonderwoerd KG, de Coo IF, Nicolay K, Prompers JJ, Smeets HJ, van Loon LJ.
Source
Departments of Genetics and Cell Biology (F.H.J.v.T., P.J.L., H.J.M.S.) and
Human Movement Sciences (L.J.C.v.L.), NUTRIM School for Nutrition, Toxicology,
and Metabolism (F.H.J.v.T., P.J.L., H.J.M.S., L.J.C.v.L.), Cardiovascular
Research Institute Maastricht (P.J.L., H.J.M.S.), and GROW-School of Oncology
and Developmental Biology (P.J.L., H.J.M.S.), Maastricht University Medical
Centre, 6200 MD Maastricht, The Netherlands; Departments of Rehabilitation
Medicine (S.F.E.P.), Clinical Genetics (K.G.C.S.), and Neurology (I.F.M.d.C.),
Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands;
Department of Diagnostic Radiology (H.M.d.F.), Magnetic Resonance Research
Center, Yale University School of Medicine, New Haven, Connecticut 06510; and
Biomedical NMR (N.M.v.d.B., J.J.P., K.N.), Department of Biomedical
Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The
Netherlands.
Abstract
Context:Conflicting data exist on mitochondrial function and physical activity
in type 2 diabetes mellitus (T2DM) development.Objective:The aim was to assess
mitochondrial function at different stages during T2DM development in
combination with physical exercise in longstanding T2DM patients.Design and
Methods:We performed cross-sectional analysis of skeletal muscle from 12
prediabetic 11 longstanding T2DM male subjects and 12 male controls matched by
age and body mass index.Intervention:One-year intrasubject controlled
supervised exercise training intervention was done in longstanding T2DM
patients.Main Outcome Measurements:Extensive ex vivo analyses of mitochondrial
quality, quantity, and function were collected and combined with global gene
expression analysis and in vivo ATP production capacity after 1 yr of training.
Results:Mitochondrial density, complex I activity, and the expression of Krebs
cycle and oxidative phosphorylation system-related genes were lower in
longstanding T2DM subjects but not in prediabetic subjects compared with
controls. This indicated a reduced capacity to generate ATP in longstanding
T2DM patients only. Gene expression analysis in prediabetic subjects suggested
a switch from carbohydrate toward lipid as an energy source. One year of
exercise training raised in vivo skeletal muscle ATP production capacity by
21?2% with an increased trend in mitochondrial density and complex I activity.
In addition, expression levels of ?-oxidation, Krebs cycle, and oxidative
phosphorylation system-related genes were higher after exercise training.
Conclusions:Mitochondrial dysfunction is apparent only in inactive longstanding
T2DM patients, which suggests that mitochondrial function and insulin
resistance do not depend on each other. Prolonged exercise training can, at
least partly, reverse the mitochondrial impairments associated with the
longstanding diabetic state.
PMID: 22802091 [PubMed - as supplied by publisher]

Source: J Clin Endocrinol Metab. 2012 Jul 16. [Epub ahead of print]

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