Chatham J C, Forder J R
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.
Am J Physiol. 1997 Jul;273(1 Pt 2):H52-8. doi: 10.1152/ajpheart.1997.273.1.H52.
The effects of streptozotocin-induced diabetes on myocardial substrate oxidation and contractile function were investigated using 13C nuclear magnetic resonance (NMR) spectroscopy. To determine the consequences of diabetes on glucose oxidation, hearts were perfused with [1-13C]glucose (11 mM) alone as well as in the presence of insulin (to stimulate glucose transport) and dichloroacetate (to stimulate pyruvate dehydrogenase). The contribution of glucose to the tricarboxylic acid (TCA) cycle was significantly decreased in hearts from diabetic animals compared with controls, with glucose alone and with insulin; however, the addition of dichloroacetate significantly increased the contribution of glucose to the TCA cycle. Contractile function in hearts from diabetic animals was significantly depressed with glucose as the sole substrate, 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 [6-13C]hexanoate (0.5 mM) as substrates. In control hearts, with glucose plus hexanoate as substrates, hexanoate contributed 98.9 +/- 2% of the substrate entering the TCA cycle; this was significantly decreased to 90.7 +/- 0.6% in the diabetic group (P < 0.02). The addition of hexanoate to the perfusate resulted in a significant increase in peak systolic pressure in the diabetic group (P < 0.001) such that contractile function was indistinguishable from controls.
使用13C核磁共振（NMR）光谱研究链脲佐菌素诱导的糖尿病对心肌底物氧化和收缩功能的影响。为了确定糖尿病对葡萄糖氧化的影响，心脏分别单独用[1-13C]葡萄糖（11 mM）以及在胰岛素（刺激葡萄糖转运）和二氯乙酸（刺激丙酮酸脱氢酶）存在的情况下进行灌注。与对照组相比，糖尿病动物心脏中葡萄糖对三羧酸（TCA）循环的贡献显著降低，无论是单独使用葡萄糖还是与胰岛素一起使用时；然而，添加二氯乙酸显著增加了葡萄糖对TCA循环的贡献。以葡萄糖作为唯一底物时，糖尿病动物心脏的收缩功能显著降低，无论是否存在胰岛素或二氯乙酸（P < 0.0005）。为了确定糖尿病是否对β-氧化和TCA循环有任何直接影响，心脏用葡萄糖（11 mM）加[6-13C]己酸（0.5 mM）作为底物进行灌注。在对照组心脏中，以葡萄糖加己酸作为底物时，己酸占进入TCA循环底物的98.9±2%；在糖尿病组中，这一比例显著降至90.7±0.6%（P < 0.02）。向灌注液中添加己酸导致糖尿病组的收缩压峰值显著升高（P < 0.001），使得收缩功能与对照组无差异。
