Isolated rat hearts were perfused according to Langendorff and as a working heart preparation with glucose as the only exogenous substrate under nonrecirculating conditions to avoid accumulation of heart metabolites and, thereby, changes in the composition of the perfusion medium. In the absence of insulin or at low work, oxidation of endogenous substrates as glycogen is of importance for myocardial energy metabolism. Accordingly, about 1/3 of the glucose oxidized by the heart was derived from myocardial glycogen. Lipolysis of endogenous triglycerides and oxidation of the fatty acids produced were, however, low in normal rat hearts. By contrast, in the presence of insulin or at high work load endogenous substrates play a minor role for energy provision. About 80% of the total oxygen consumption could be attributed to the oxidation of exogenous glucose. Furthermore, insulin exerted its major effect in accelerating glucose uptake and glycolysis, but had little influence on PDH-activity. Insulin increased lipolysis in control hearts, however, changes in the endogenous triglycerides were less than valves calculated from the rate of lipolysis. Thus, glycerol release can be taken as a measure for lipolysis, but not as a measure for fatty acid oxidation, since the produced fatty acids were partly reesterified to glycerides. On the basis of the metabolic data obtained, the oxygen and energy balance was calculated. We conclude that a sufficient energy provision is only warranted if the rat heart is perfused either in the presence of insulin or at higher--more physiological--work load.

Adenosine Triphosphate↗

PubMedDate not supplied

Insulin receptors on isolated heart cells: effect of temperature and hydrolytic enzymes.

Isolated muscle cells from adult rat heart have been used to study the effect of temperature and enzymic digestion on the binding of 125I-labelled insulin. Equilibrium binding studies were performed at both 4 and 37 degrees C, using insulin concentrations ranging from 2.5 X 10(-11) mol/l to 10(-6) mol/l. The empty site affinity constant decreased by 51% from 1.0 X 10(8) l/mol at 4 degrees C to 4.9 X 10(7) l/mol at 37 degrees C, whereas the total receptor concentration remained unaltered at both temperatures. The rate of dilution induced dissociation was enhanced by the presence of native insulin at 37 degrees C, confirming the presence of negative cooperativity among the receptor sites at physiological temperatures. Treatment of isolated heart cells with trypsin and beta-galactosidase led to a decrease in specific binding of 125I-labelled insulin. Myocytes treated with neuraminidase exhibited a significant increase in insulin binding, which was shown to be due to an increase in insulin-receptor affinity. These studies provide new information on the molecular characteristics of insulin receptors in the heart muscle.

Animals↗

PubMedDate not supplied

Myocardial performance and metabolism in non-ketotic, diabetic rat hearts: myocardial function and metabolism in vivo and in the isolated perfused heart under the influence of insulin and octanoate.

The influence of a non-ketonic, chronically diabetic state (60 mg/kg streptozotocin) on cardiac function and metabolism was studied under in vivo conditions by inserting a Millar-tip catheter into the left ventricle and in the model of the isolated perfused heart. In vivo heart rate and maximal left ventricular systolic pressure were reduced after a diabetes duration of 4 and 12 weeks. The maximal rise and fall in left ventricular pressure progressively declined with the duration of diabetes. The reduced myocardial function was associated with a loss in ATP and adenine nucleotides. In the perfused heart of chronically diabetic rats, heart function was also impaired and could not be restored in vitro by perfusion with glucose and insulin. In the presence of octanoate--a substrate which can be metabolized independently from insulin--heart function of diabetic rats was improved, but remained lowered as compared to controls. Since the content of myocardial creatine phosphate was reduced in diabetic hearts perfused with octanoate, these findings indicate that the suppression of cardiac performance is not only a result of an impaired glucose metabolism, but of a more general defect in energy provision and utilization. In contrast to hearts of acutely diabetic, ketotic rats most often used, the rate of lipolysis of endogenous triglycerides and the contribution of fatty acids to energy production was low in the chronically diabetic state. Inhibition of fatty acid oxidation by an inhibitor of carnitine palmitoyltransferase (CPTI) did not restore the reduced responsiveness of diabetic hearts to insulin. Analysis of intracardiac metabolites revealed that in the perfused heart of chronically diabetic rats glucose-6-phosphate and citrate do not accumulate as in hearts of ketotic, diabetic rats. Therefore, the impaired glucose metabolism presumably reflects a reduced uptake of glucose rather than in inhibition of glycolysis as in hearts of ketotic, diabetic rats.

Animals↗