Upregulation of PPARbeta/delta is associated with structural and functional changes in the type I diabetes rat diaphragm.
BACKGROUND
Diabetes mellitus is associated with alterations in peripheral striated muscles and cardiomyopathy. We examined diaphragmatic function and fiber composition and identified the role of peroxisome proliferator-activated receptors (PPAR alpha and beta/delta) as a factor involved in diaphragm muscle plasticity in response to type I diabetes.


RESULTS
Streptozotocin-treated rats were studied after 8 weeks and compared with their controls. Diaphragmatic strips were stimulated in vitro and mechanical and energetic variables were measured, cross bridge kinetics assessed, and the effects of fatigue and hypoxia evaluated. Morphometry, myosin heavy chain isoforms, PPAR alpha and beta/delta gene and protein expression were also assessed. Diabetes induced a decrease in maximum velocity of shortening (-14%, P<0.05) associated with a decrease in myosin ATPase activity (-49%, P<0.05), and an increase in force (+20%, P<0.05) associated with an increase in the number of cross bridges (+14%, P<0.05). These modifications were in agreement with a shift towards slow myosin heavy chain fibers and were associated with an upregulation of PPARbeta/delta (+314% increase in gene and +190% increase in protein expression, P<0.05). In addition, greater resistances to fatigue and hypoxia were observed in diabetic rats.


CONCLUSIONS
Type I diabetes induced complex mechanical and energetic changes in the rat diaphragm and was associated with an up-regulation of PPARbeta/delta that could improve resistance to fatigue and hypoxia and favour the shift towards slow myosin heavy chain isoforms.
Salvi
Nadège
N
UMRS INSERM 956, Institut de Myologie, IFR14, Université Pierre et Marie Curie-Paris 6, and Department of Emergency Medicine and Surgery, Groupe hospitalier Pitié-Salpêtrière, Assistance Publique-Hôptiaux de Paris, Paris, France.
Guellich
Aziz
A
Michelet
Pierre
P
Demoule
Alexandre
A
Le Guen
Morgan
M
Renou
Laure
L
Bonne
Gisèle
G
Riou
Bruno
B
Langeron
Olivier
O
Coirault
Catherine
C
D000818:Animals; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005221:Fatigue / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009218:Myosins / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D047494:PPAR delta; D048068:PPAR-beta; D009218:Myosins