Exercise improves impaired ventricular function and alterations of cardiac myofibrillar proteins in diabetic dyslipidemic pigs.
Chronic diabetes is often associated with cardiomyopathy, which may result, in part, from defects in cardiac muscle proteins. We investigated whether a 20-wk porcine model of diabetic dyslipidemia (DD) would impair in vivo myocardial function and yield alterations in cardiac myofibrillar proteins and whether endurance exercise training would improve these changes. Myocardial function was depressed in anesthetized DD pigs (n = 12) compared with sedentary controls (C; n = 13) as evidenced by an approximately 30% decrease in left ventricular fractional shortening and an approximately 35% decrease in +dP/dt measured by noninvasive echocardiography and direct cardiac catheterization, respectively. This depression in myocardial function was improved with chronic exercise as treadmill-trained DD pigs (DDX) (n = 13) had significantly greater fractional shortening and +dP/dt than DD animals. Interestingly, the isoform expression pattern of the myofibrillar regulatory protein, cardiac troponin T (cTnT), was significantly shifted from cTnT1 toward cTnT2 and cTnT3 in DD pigs. Furthermore, this change in cTnT isoform expression pattern was prevented in DDX pigs. Finally, there was a decrease in baseline levels of cAMP-dependent protein kinase-induced phosphorylation of the myofibrillar proteins troponin I and myosin-binding protein-C in DD animals. Overall, these results indicate that 20 wk of DD lead to myocardial dysfunction coincident with significant alterations in myofibrillar proteins, both of which are prevented with endurance exercise training, implying that changes in myofibrillar proteins may contribute, at least in part, to cardiac dysfunction associated with diabetic cardiomyopathy.
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, USA.
F Steven
FS
Korte
Eric A
EA
Mokelke
Michael
M
Sturek
Kerry S
KS
McDonald
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D005081:Exercise Therapy / Q000379:methods*; D006949:Hyperlipidemias / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010807:Physical Endurance; D020033:Protein Isoforms / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D013552:Swine; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*
D009124:Muscle Proteins; D020033:Protein Isoforms