Law W R, McLane M P
Department of Surgery, University of Illinois at Chicago Medical Center 60612, USA.
Cardiovasc Res. 1996 May;31(5):691-8. doi: 10.1016/0008-6363(95)00243-X.
We have demonstrated that adenosine enhances insulin-stimulated myocardial glucose uptake in situ. In the present study we determined the role of adrenergic influences and myocardial work on insulin-stimulated myocardial glucose uptake while varying intracoronary adenosine concentrations. Under pentobarbital anesthesia we instrumented mongrel dogs to obtain blood pressure, 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 myocardial oxygen (MVO2) and glucose (MGU) uptakes. Somatostatin was infused i.v. (0.8 microgram/kg.min-1) along with 10 mU/kg.min-1 regular insulin, and variable quantities of glucose to maintain euglycemia. Adenosine was infused at logarithmic incremental rates (0, 0.01, 0.1, 1.0, and 10 mumoles.min-1) for 30 min each into the main left coronary arteries. Adrenergic blockade was achieved with i.v. propranolol (70 micrograms/kg bolus followed by 5 micrograms/kg.min-1 infusion), and phentolamine (95 micrograms/kg bolus followed by 9.5 micrograms/kg.min-1 infusion). Insulin infusion significantly increased MGU. Adenosine increased the maximal value for insulin-stimulated glucose uptake. Adrenergic blockade alone did not alter insulin-stimulated MGU, but reduced heart rate and MVO2. When evaluated relative to MVO2 1.0 mumoles/ml adenosine infusion increased MGU independent of work-related changes in the presence or absence of adrenergic blockade. With an adenosine infusion rate of 10 mumoles/ml myocardial glucose uptake returned to baseline. These data also support our earlier speculation that the MGU response to adenosine may be biphasic. These results suggest that antagonism of adrenergic effects by adenosine cannot account for adenosine's ability to enhance insulin's effects on glucose uptake in the heart, but that work-related influences should be accounted for in interpreting results of this kind.
我们已经证明，腺苷可增强胰岛素刺激的心肌原位葡萄糖摄取。在本研究中，我们在改变冠状动脉内腺苷浓度的同时，确定了肾上腺素能影响和心肌做功对胰岛素刺激的心肌葡萄糖摄取的作用。在戊巴比妥麻醉下，我们对杂种犬进行仪器植入，以获取血压、心率以及动脉和冠状窦血样，用于测量氧气和葡萄糖浓度。围绕左旋冠状动脉的电磁血流探头可测定血流量，并计算心肌氧摄取量（MVO2）和葡萄糖摄取量（MGU）。静脉输注生长抑素（0.8微克/千克·分钟-1）以及10微单位/千克·分钟-1的正规胰岛素，并输注不同量的葡萄糖以维持血糖正常。以对数递增速率（0、0.01、0.1、1.0和10微摩尔/分钟-1）将腺苷分别输注到左冠状动脉主干中，每次输注30分钟。通过静脉注射普萘洛尔（70微克/千克推注，随后以5微克/千克·分钟-1输注）和酚妥拉明（95微克/千克推注，随后以9.5微克/千克·分钟-1输注）实现肾上腺素能阻断。胰岛素输注显著增加了MGU。腺苷增加了胰岛素刺激的葡萄糖摄取的最大值。单独的肾上腺素能阻断并未改变胰岛素刺激的MGU，但降低了心率和MVO2。当相对于MVO2进行评估时，在存在或不存在肾上腺素能阻断的情况下，输注1.0微摩尔/毫升腺苷均可增加MGU，且与做功相关的变化无关。当腺苷输注速率为10微摩尔/毫升时，心肌葡萄糖摄取恢复到基线水平。这些数据也支持了我们早期的推测，即MGU对腺苷的反应可能是双相的。这些结果表明，腺苷对肾上腺素能效应的拮抗作用不能解释腺苷增强胰岛素对心脏葡萄糖摄取作用的能力，但在解释此类结果时应考虑做功相关的影响。
