Mokuda O, Sakamoto Y, Ikeda T, Mashiba H
Third Department of Internal Medicine, Teikyo University School of Medicine, Chiba, Japan.
Ann Nutr Metab. 1990;34(5):259-65. doi: 10.1159/000177596.
To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization.
为研究糖尿病心脏中的无氧糖酵解和葡萄糖氧化，我们研究了缺氧和低外源性游离脂肪酸（FFA）对链脲佐菌素诱导的糖尿病大鼠离体灌注心脏中心肌三磷酸腺苷（ATP）含量的影响。灌注液由含5 mM葡萄糖和0.30 mM或0.05 mM FFA的 Krebs-Ringer缓冲液（pH 7.4）组成，用95% O₂ + 5% CO₂ 或95% N₂ + 5% CO₂ 气体平衡。在有氧条件下，糖尿病心脏的葡萄糖摄取、乳酸生成和葡萄糖氧化分别比对照组降低了68%、57%和53%，而糖尿病心脏的FFA氧化比对照组增加了67%。在缺氧条件下，糖尿病心脏葡萄糖摄取和乳酸生成的增加量远小于对照组（分别为2.6和9.5 μmol/g/30 min，而对照组为11.4和40 μmol/g/30 min）。糖尿病心肌中的ATP含量在缺氧灌注时比对照组下降得更快。在有氧灌注中，对照组心肌中的ATP含量在灌注液中低FFA（0.05 mM）时可维持60分钟。糖尿病心肌中的ATP含量在低FFA条件下40分钟后降低，但通过添加0.30 mM FFA可良好维持60分钟。因此，当外源性FFA供应耗尽时，有氧糖尿病心肌中的ATP含量不能得到良好维持。这些结果表明，糖尿病心脏在糖酵解和葡萄糖氧化的刺激方面存在原发性缺陷，这并非由FFA利用增加所致。
