N. Takeda et al., SEQUENCE OF ALTERATIONS IN SUBCELLULAR ORGANELLES DURING THE DEVELOPMENT OF HEART DYSFUNCTION IN DIABETES, Diabetes research and clinical practice, 30, 1996, pp. 113-122
Although changes in different subcellular organelles such as myofibril
s, sarcoplasmic reticulum (SR), mitochondria and sarcolemma (SL), as w
ell as in heart function have been reported to occur in chronic diabet
es, their inter-relationships and functional significance are poorly u
nderstood, In order to gain information on this aspect, diabetes in ra
ts was induced by an intravenous injection of streptozotocin and anima
ls were assessed hemodynamically at 15-27 days. Ventricular tissue fro
m several diabetic animals was pooled, subcellular organelles were iso
lated and their biochemical activities determined. Significant depress
ions in cardiac contractile and relaxation were observed to be associa
ted with decreases in myofibrillar Ca2+- stimulated ATPase and SR Ca2-pump activities at 21 days from the induction of diabetes, Likewise,
the SL Na+-Ca2+ exchange and Ca2+-channel density were decreased at 21
days but the affinity of SL Ca2+-channels was increased in the diabet
ic heart. The SL Ca2+-pump and Na+-K+ ATPase activities were depressed
at 18 and 24 days, respectively. Both alpha- and beta-adrenoceptor de
nsities in SL were decreased at 27 days whereas no changes in mitochon
drial function were observed at these early stages of diabetes. The SL
low affinity Ca2+-binding was decreased while the low affinity Ca2+-A
TPase activity was increased at 18 days following the induction of dia
betes. These results indicate that SL defects precede those in SR, myo
fibrils or mitochondria and suggest that abnormalities in Ca2+-handlin
g as well as interaction of Ca2+ with myofilaments in cardiomyocytes m
ay lead to the development of heart dysfunction in chronic diabetes.