Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients.
BACKGROUND
Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients.


METHODS
We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period.


RESULTS
This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters.


CONCLUSIONS
This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.
Fritz
Tomas
T
Centre of Family Medicine, Karolinska University Hospital, Karolinska Institutet, 171 11 Stockholm, Sweden.
Krämer
David K
DK
Karlsson
Håkan K R
HK
Galuska
Dana
D
Engfeldt
Peter
P
Zierath
Juleen R
JR
Krook
Anna
A
D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D019852:Diacylglycerol Kinase / Q000096:biosynthesis; D015444:Exercise / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis; D047494:PPAR delta / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D000071247:Uncoupling Protein 3
D003598:Cytoskeletal Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D047494:PPAR delta; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; C497139:DGKD protein, human; D019852:Diacylglycerol Kinase