Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes.
BACKGROUND
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.


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.


METHODS
One-year intrasubject controlled supervised exercise training intervention was done in longstanding T2DM patients.


METHODS
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 β-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.
Department of Genetics and Cell Biology, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
F H J
FH
van Tienen
S F E
SF
Praet
H M
HM
de Feyter
N M
NM
van den Broek
P J
PJ
Lindsey
K G C
KG
Schoonderwoerd
I F M
IF
de Coo
K
K
Nicolay
J J
JJ
Prompers
H J M
HJ
Smeets
L J C
LJ
van Loon
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D002952:Citric Acid Cycle / Q000235:genetics / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000628:therapy*; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010809:Physical Fitness / Q000502:physiology; D011236:Prediabetic State / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D000255:Adenosine Triphosphate