210
storage enzyme) [ 46 ]. Bilet et al. [ 47 ] demonstrated that acute bout of exercise
increased plasma FFAs levels and cardiac lipid, without hampering systolic func-
tion in healthy subjects. On the other hand, endurance training reduced myocardial
TAG and improved ejection fraction in obese subjects [ 48 ]. However, in obese type
2 diabetic patients, endurance training didn’t alter myocardial TAG [ 49 ]. A recent
study conducted by Hojan et al. [ 50 ] showed significant improvement in cardio-
metabolic markers in prostate cancer men after a trial of a 12-month exercise pro-
gram. In addition, Mandrup et al. [ 51 ] demonstrated reduced risk factors for type 2
DM and cardiovascular disease after high-intensity aerobic training in premeno-
pausal and postmenopausal women. Furthermore, myocardial TAG content has
been reduced in diet-induced obese mice subjected to exercise [ 33 ]. Of note, acute
exercise has been reported to increase the expression of Perilipin-5 (Plin-5) in
human skeletal muscle [ 52 ]. Plin-5 is believed to facilitate and stabilize lipolysis in
the cardiomyocyte and to play a role in the direct transfer of fatty acids between
lipid droplets and mitochondria [ 53 ]. Plin-5 knockout mice showed resistance to
STZ-induced cardiac dysfunction [ 54 ]. However, the role of exercise on Plin-5 in
the diabetic heart remains to be explored.
4 Exercise Alleviates Cardiac Insulin Signaling and Glucose
Metabolism
Type 2 DM is characterized by insulin resistance which manifests the heart and
provokes cardiac contractile dysfunction [ 55 ]. However, less is known about the
mechanisms underlying the impact of insulin resistance on cardiac dysfunction
[ 56 ]. This poor understanding is attributed to the association of insulin resistance
and hyperglycemia with hyperlipidemia, fluctuations in hormones and obesity in the
available type 2 DM models. Therefore, teasing out the direct effects of insulin
resistance on cardiac function is difficult [ 57 ]. Boudina et al. [ 58 ] stated that insulin
receptor deletion in cardiomyocyte of the CIRKO mouse model would help to trace
out the exact impact of insulin resistance on cardiac function.
Diabetes has been reported to preserve the Ras-mitogen-activated protein kinase(Ras/MAPK)-dependent pathway, while impairing the phosphoinositide 3-kinase
(PI3K)-mediated pro-survival signaling cascade [ 59 – 61 ], favoring the atherogenic
and mitogenic actions of insulin [ 62 ]. Through activation of the c-Jun N-terminal
kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK) [ 63 , 64 ],
the Ras/MAPK-dependent pathway can promote cell differentiation and apoptosis
[ 65 ]. On the other hand, impaired phosphorylation of IRS-1 in diabetes and insulin
resistance negatively affects the PI3K/PDK1/Akt/aPKC pathway and consequently
decreased nitric oxide (NO) bioavailability [ 66 ], lipid metabolism [ 67 ] and translo-
cation of the glucose transporters (GLUT) -1 and -4 [ 68 ].
A.M. Mahmoud