The metabolism of endogenous triacylglycerols (TG) was studied in perfused working hearts of control and 12-day-old streptozotocin-treated diabetic rats. TG synthesis was assessed by the incorporation of exogenous [9,10(-3)H]palmitate. TG lipolysis was assessed by the following two methods: 1) measurement of the decrease in [14C]TG after prior in vivo isotopic prelabeling with [1-14C]palmitate and 2) calculation of the change in TG content as TG synthesis minus TG lipolysis. Control and diabetic hearts were perfused with buffer containing substrate concentrations characteristic of the in vivo state [normal: 9 mM glucose, 0.5 mM free fatty acid (FFA); diabetic: 27 mM glucose, 1.2 mM FFA]. Diabetic hearts were also perfused under normal substrate conditions. In diabetic hearts perfused under diabetic conditions elevated TG levels were maintained, lipolysis was reduced or unchanged (depending on the method of determination), and synthesis was enhanced. Oxidation of TG fatty acids (TGFA) was not impaired. Control hearts showed net lipolysis coupled with lower rates of exogenous FFA uptake and TG synthesis. In diabetic hearts perfused under normal substrate conditions lipolysis and TGFA oxidation were markedly enhanced. Thus we suggest that the basis of TG accumulation seen in the diabetic heart is due to both inhibition of lipolysis and enhancement of synthesis resulting from high levels of exogenous FFA and glucose.
The effects of epinephrine and norepinephrine on triglyceride and glycogen metabolism and contractility were studied in isolated perfused working rat hearts. Hearts with lipids prelabeled in vivo with [1-14C]palmitate were perfused with bicarbonate buffer containing 5.5 mM glucose, with or without 0.6 mM palmitate (3% albumin), and varying concentrations of catecholamines. Direct evidence for catecholamine-stimulated myocardial triglyceride lipolysis was obtained and, for the first time, was shown to be concentration-dependent. Also, catecholamines enhanced heart triglyceride fatty acid oxidation in concentration-dependent fashion. Stimulation of lipolysis and oxidation was observed only in hearts perfused with buffer containing glucose as the sole substrate, and was inhibited in the presence of 0.6 mM palmitate. Palmitate inhibited net glycogenolysis in the absence of catecholamines, but had little effect on epinephrine-stimulated glycogenolysis. Therefore, with free fatty acids present, mobilization of endogenous triglycerides to meet the increased metabolic demands of catecholamine stimulation is minimized; this is due, possibly, to enhanced utilization of exogenous free fatty acids and to inhibition of net lipolysis.
Injection of synthetic bovine parathyroid hormone (the amino terminal peptide containing the first 34 amino acids) to the coronary circulation of the dog resulted in a marked coronary vasodilation. The vasodilatory response was dose-dependent and amounted to a 161 percent increase over the resting flow rate at a concentration of 1.0 unit per kilogram.
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