Yoshifumi Awaji

1,2-Diacylglycerol Content and Its Fatty Acid Composition in Thoracic Aorta of Diabetic Rats

These experiments were conducted to determine 1,2-diacylglycerol (DAG) in the thoracic aorta obtained from streptozocin-induced diabetic rats because 1,2-DAG is assumed to be a second messenger associated with phosphoinositide metabolism. After preincubation for a 25-min stabilization, 1,2-DAG content in isolated thoracic aortas 4 and 8 wk after streptozocin injection was significantly decreased by 42 and 31%, respectively, compared with age-matched control rats on 10-min norepinephrine stimulation (10−5 M). However, 4 wk of daily insulin injection after 4 wk of untreated diabetes significantly shifted 1,2-DAG toward normal levels. Analysis of its fatty acid composition showed a significant difference between control and diabetic rat aortas at both 4 and 8 wk. In particular, the percentage of arachidonate, a precursor of eicosanoids, decreased. Such alteration in the fatty acid profile in diabetic rat aortas was inhibited by insulin treatment. 1,2-DAG content in the 8-wk diabetic group was also significantly decreased by 33% compared with control in the absence of norepinephrine, whereas 1,2-DAG content was lower than in the presence of norepinephrine in both the control and diabetic groups. Cholesterol, triglyceride, and phosphatidylcholine content in diabetic rat aortas was lower than control. Lower levels of 1,2-DAG in the thoracic aorta from diabetic rats were observed in the presence and absence of norepinephrine, suggesting that a defect in 1,2-DAG production may be associated with abnormalities of vascular smooth muscle responsiveness by agonists, as described previously.

Myocardial Isoenzyme Distribution in Chronic Diabetes: Comparison with Isoproterenol-Induced Chronic Myocardial Damage

In the chronically diabetic heart, it has been reported that the activity of several enzymes bound to cell structures, such as sarcoplasmic reticular Ca++ ATPase, sarcolemmal Na+-K+ ATPase and myosin ATPase is depressed and that the isoenzyme distribution of myosin ATPase is altered (1,2). However, the changes in the activity and isoenzyme distribution of creatine kinase (CK: EC 2.7.3.2) and lactate dehydrogenase (LD: EC 1.1.1.27) which are mainly “soluble” enzymes and clinically important markers of myocardial necrosis (3) have not been reported in the diabetic heart previously. Therefore, in this study we measured total and isoenzyme activities of myocardial CK and LD in rats with insulin dependent diabetes and compared them with control. Since intracellular calcium overload has been suggested in the pathogenesis of diabetic cardiomyopathy (1,2,4), we also measured the activity of the same (iso)enzymes in the myocardium of rats chronically injected with isoproterenol, a pure s-adrenergic stimulant, which develop cardiomyopathy with intracellular calcium overload (5).