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The effects of insulin and β-adrenergic stimulation on glucose transport, glut 4 and PKB activation in the myocardium of lean and obese non-insulin dependent diabetes mellitus rats

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Abstract

Glucose uptake, glut 4 translocation and activation of protein kinase B were measured in Langendorff perfused hearts from (i) Wistar control, (ii) lean, neonatal Streptozotocin induced (Stz) and (iii) Zucker (fa/fa) obese diabetic rats of 10–12 weeks old. Hearts were subjected to stimulation with insulin, isoproterenol (β-adrenergic agonist) or a combination of insulin and isoproterenol, during the perfusion protocol. Basal myocardial glucose uptake was impaired in both diabetic models, but could be stimulated significantly by insulin. In the Zucker rats, the time-course of insulin action was delayed. Insulin and β-stimulation of glucose uptake were not additive. Evaluation of sarcolemmal membranes from these hearts showed that the affinity of glut 4 was significantly lower in the Zucker but not in the Stz hearts while a reduced affinity found with a combination of insulin and β-stimulation in control hearts, was absent in both diabetic models. Total membrane lysates were analyzed for glut 4 expression while an intracellular component was generated to quantify translocation on stimulation as well as activity of protein kinase B (PKB). At this age, the neonatal Streptozotocin induced diabetic animals presented with more faulty regulation concerning adrenergic stimulated effects on elements of this signal transduction pathway while the Zucker fa/fa animals showed larger deviations in insulin stimulated effects. The overall response of the Zucker myocardium was poorer than that of the Stz group. No significant modulation of β-adrenergic signaling on insulin stimulated glucose uptake was found. The PI-3-kinase inhibitor wortmannin, could abolish glucose uptake as well as PKB activation elicited by both insulin and isoproterenol.

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Authors and Affiliations

  1. Department of Medical Physiology and Biochemistry, P.O. Box 19063, Tygerberg, 7505

    Magdalena van Zyl, Alana Keyser & Amanda Lochner

  2. MRC Programme for Experimental Biology, Tygerberg, Republic of South Africa

    Barbara Huisamen, Magdalena van Zyl, Alana Keyser & Amanda Lochner

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  1. Barbara Huisamen
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  2. Magdalena van Zyl
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  4. Amanda Lochner
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Correspondence to Barbara Huisamen.

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Huisamen, B., van Zyl, M., Keyser, A. et al. The effects of insulin and β-adrenergic stimulation on glucose transport, glut 4 and PKB activation in the myocardium of lean and obese non-insulin dependent diabetes mellitus rats. Mol Cell Biochem 223, 15–25 (2001). https://doi.org/10.1023/A:1017528402205

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