Xu Y, Lu L, Zhu P, Schwartz G G
Cardiovascular Research Institute, University of California, San Francisco, California 94121, USA.
Am J Physiol. 1998 Dec;275(6):H2181-90. doi: 10.1152/ajpheart.1998.275.6.H2181.
At steady state, a balance is expected between net myocardial uptake of the principal exogenous carbon substrates and the rate at which these substrates are metabolized. Such a balance is present when the sum of the oxygen extraction ratios (OERs) for glucose, lactate, and free fatty acids (FFA) is near unity. We have previously observed that systemic administration of the beta-adrenergic agonist isoproterenol (Iso) induces a state of excess myocardial substrate uptake relative to the rate of substrate metabolism, reflected by a sum of OERs significantly >1.0. This occurs in conjunction with an Iso-stimulated increase in circulating insulin levels. The goal of the present study was to determine whether this excess substrate uptake depends on the effects of insulin and time. In open-chest anesthetized pigs, myocardial blood flow, substrate uptake, and oxygen consumption were measured at baseline and during systemic administration of Iso (0.08 microgram. kg-1. min-1 iv) under the following conditions: group 1 (n = 10), normal endogenous insulin release; group 2 (n = 10), inhibition of endogenous insulin release with somatostatin; group 3 (n = 7), at 45 and 90 min Iso; group 4 (n = 7), at 45 and 90 min Iso, with exogenous insulin given during the latter measurement. In group 1, plasma insulin rose fivefold with Iso while the sum of the OERs for glucose, lactate, and FFA increased from 0.92 +/- 0.21 at baseline to 1.57 +/- 0.17 with Iso (P < 0.01). In group 2, somatostatin blunted the increase in insulin with Iso and there was no significant change in the sum of OERs between baseline and Iso. In group 3, the sum of OERs increased from 0.95 +/- 0.11 at baseline to 1.69 +/- 0.20 at 45 min Iso (P < 0.01), similar to the response of group 1. However, the state of excess substrate uptake was transient; by 90 min Iso the sum of OERs declined to 0.69 +/- 0.21 (P < 0.05 vs. 45 min Iso). In group 4, excess substrate uptake could not be sustained at 90 min Iso despite administration of exogenous insulin. Systemic beta-adrenergic stimulation causes a transient condition of myocardial substrate uptake in excess of metabolism. Increased plasma insulin is necessary to produce this condition, but a high insulin level does not prolong the condition.
在稳态下，预计主要外源性碳底物的心肌净摄取量与这些底物的代谢速率之间会达到平衡。当葡萄糖、乳酸和游离脂肪酸（FFA）的氧摄取率（OER）之和接近1时，就存在这种平衡。我们之前观察到，全身给予β-肾上腺素能激动剂异丙肾上腺素（Iso）会导致心肌底物摄取相对于底物代谢速率处于过剩状态，这表现为OER之和显著>1.0。这种情况与Iso刺激引起的循环胰岛素水平升高同时发生。本研究的目的是确定这种底物摄取过剩是否取决于胰岛素的作用和时间。在开胸麻醉的猪中，在以下条件下于基线时以及全身给予Iso（0.08微克·千克⁻¹·分钟⁻¹静脉注射）期间测量心肌血流量、底物摄取和氧消耗：第1组（n = 10），内源性胰岛素正常释放；第2组（n = 10），用生长抑素抑制内源性胰岛素释放；第3组（n = 7），在Iso给药45分钟和90分钟时测量；第4组（n = 7），在Iso给药45分钟和90分钟时测量，且在后者测量期间给予外源性胰岛素。在第1组中，Iso使血浆胰岛素升高了5倍，同时葡萄糖、乳酸和FFA的OER之和从基线时的0.92±0.21增加到Iso给药时的1.57±0.17（P<0.01）。在第2组中，生长抑素减弱了Iso引起的胰岛素升高，并且基线与Iso给药之间OER之和没有显著变化。在第3组中，OER之和从基线时的0.95±0.11增加到Iso给药45分钟时的1.69±0.20（P<0.01），与第1组的反应相似。然而，底物摄取过剩的状态是短暂的；到Iso给药90分钟时，OER之和降至0.69±0.21（与Iso给药45分钟时相比，P<0.05）。在第4组中，尽管给予了外源性胰岛素，但在Iso给药90分钟时仍无法维持底物摄取过剩。全身β-肾上腺素能刺激会导致心肌底物摄取超过代谢的短暂状态。血浆胰岛素升高是产生这种状态所必需的，但高胰岛素水平并不会延长这种状态。
