RELATIONSHIP BETWEEN CARDIAC-FUNCTION AND SUBSTRATE OXIDATION IN HEARTS OF DIABETIC RATS

The effects of streptozotocin-induced diabetes on myocardial substrate oxidation and contractile function were investigated using C-13 nucle ar magnetic resonance (NMR) spectroscopy. To determine the consequence s of diabetes on glucose oxidation, hearts were perfused with [1-C-13] glucose (11 mM) alone as well as in the presence of insulin ito stimul ate glucose transport) and dichloroacetate itc, stimulate pyruvate deh ydrogenase). The contribution of glucose to the tricarboxylic acid (TC A) cycle was significantly decreased in hear ts from diabetic animals compared with controls, with glucose alone and with insulin; however, the addition of dichloroacetate significantly increased the contributi on of glucose to the TCA cycle. Contractile function in hearts from di abetic animals was significantly depressed with glucose as the sole su bstrate, regardless of the presence of insulin or dichloroacetate (P < 0.0005). To determine whether diabetes had any direct effects on beta -oxidation and the TCA cycle, hearts were perfused with glucose (11 mM ) plus [6-C-13]hexanoate (0.5 mM) as substrates. In control hearts, wi th glucose plus hexanoate as substrates, hexanoate contributed 98.9 +/ - 2% of the substrate entering the TCA cycle; this was significantly d ecreased to 90.7 +/- 0.6% in the diabetic group (P < 0.02). The additi on of hexanoate to the perfusate resulted in a significant increase in peak systolic pressure in the diabetic group (P < 0.001) such that co ntractile function was indistinguishable from controls.