Law W R, McLane M P
Department of Surgery, Loyola University Medical Center, Maywood, IL.
Metabolism. 1991 Sep;40(9):947-52. doi: 10.1016/0026-0495(91)90071-4.
Better understood in other tissues, the effects of adenosine on insulin-stimulated glucose uptake in the heart are poorly understood. Under pentobarbital anesthesia, we instrumented mongrel dogs to obtain general hemodynamics (blood pressure and heart rate), and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of substrate uptake by the heart (Fick principle). Somatostatin (SRIF) was infused intravenously (0.8 micrograms/kg/min) along with 0, 0.5, 1.0, 5.0, or 10 mU/kg/min regular insulin, and variable quantities of glucose to maintain euglycemia. Concomitant with the SRIF, insulin, and glucose infusions, adenosine was infused in logarithmically increasing rates (0, 0.01, 0.1, 1.0, 10 or 100 mumol/min) for 30 minutes each into the main left coronary arteries. Insulin infusions increased myocardial glucose uptake in a dose-dependent manner. The heart displayed exquisite sensitivity to insulin, with an ED50 of approximately 14 microU/mL (serum insulin). Adenosine infusions in the absence of insulin (SRIF infusion) increased coronary blood flow, but did not alter myocardial glucose uptake. In the presence of insulin, adenosine increased the maximal value for glucose uptake without changing sensitivity to insulin. These results indicate that adenosine enhances myocardial responsiveness to insulin, with respect to glucose uptake, independent of changes in blood flow. Since glucose can be used for anaerobic metabolism, and adenosine levels are known to increase under situations in which myocardial oxygenation is inadequate, these data have serious implications for conditions such as myocardial ischemia or hypoxia, when glycolytic substrate availability is vital.
腺苷对心脏中胰岛素刺激的葡萄糖摄取的影响在其他组织中已得到较好理解，但在心脏中却了解甚少。在戊巴比妥麻醉下，我们对杂种犬进行仪器植入以获取一般血流动力学参数（血压和心率），并采集动脉和冠状窦血样以测量氧气和葡萄糖浓度。围绕左旋冠状动脉放置的电磁血流探头可测定血流量，并根据菲克原理计算心脏对底物的摄取量。静脉内输注生长抑素（SRIF，0.8微克/千克/分钟），同时分别输注0、0.5、1.0、5.0或10毫单位/千克/分钟的正规胰岛素以及可变数量的葡萄糖以维持血糖正常。在输注SRIF、胰岛素和葡萄糖的同时，以对数递增速率（0、0.01、0.1、1.0、10或100微摩尔/分钟）向左冠状动脉主干内输注腺苷，每次持续30分钟。胰岛素输注以剂量依赖方式增加心肌葡萄糖摄取。心脏对胰岛素表现出极高的敏感性，半数有效剂量（ED50）约为14微单位/毫升（血清胰岛素）。在无胰岛素（输注SRIF）的情况下输注腺苷可增加冠状动脉血流量，但不改变心肌葡萄糖摄取。在有胰岛素存在时，腺苷增加了葡萄糖摄取的最大值，但不改变对胰岛素的敏感性。这些结果表明，腺苷在葡萄糖摄取方面增强了心肌对胰岛素的反应性，且与血流量变化无关。由于葡萄糖可用于无氧代谢，且已知在心肌氧合不足的情况下腺苷水平会升高，因此这些数据对于诸如心肌缺血或缺氧等情况具有重要意义，因为此时糖酵解底物的可用性至关重要。
