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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

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Summary

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 glucolysis as in hearts of ketotic, diabetic rats.

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  1. P. Rösen

    Present address: Diabetesforschungsinstitut an der Universität Düsseldorf, Auf'm Hennekamp 65, D-4000, Düsseldorf, FRG

Authors and Affiliations

  1. Diabetesforschungsinstitut an der Universität Düsseldorf, Auf'm Hennekamp 65, D-4000, Düsseldorf, FRG

    P. Windeck & H. Reinauer

  2. Physiologisches Institut an der Universität München, FRG

    H. -G. Zimmer

  3. Pathologisches Institut an der Universität Düsseldorf, FRG

    H. Frenzel & K. F. Bürrig

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Rösen, P., Windeck, P., Zimmer, H.G. et al. 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. Basic Res Cardiol 81, 620–635 (1986). https://doi.org/10.1007/BF02005186

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  • DOI: https://doi.org/10.1007/BF02005186

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