Randle P J, Priestman D A, Mistry S, Halsall A
Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, UK.
Diabetologia. 1994 Sep;37 Suppl 2:S155-61. doi: 10.1007/BF00400839.
The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal muscles. Such short term effects have since been extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also been convincingly demonstrated in man in vivo. More recently a longer term effect of fatty acid metabolism to decrease glucose oxidation (hours) has been shown in heart and skeletal muscle and liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspects of glucose metabolism could be important in the development of insulin resistance in diabetes mellitus in man.
30年前提出并在1966年的明可夫斯基讲座中进行回顾的葡萄糖脂肪酸循环描述了脂肪酸的短期效应（数分钟），即降低心脏和骨骼肌对葡萄糖的摄取、糖酵解及氧化。此后，这种短期效应已扩展至包括抑制肝脏对葡萄糖的摄取和糖酵解以及刺激糖异生，并且这些效应也已在人体中得到令人信服的证实。最近，脂肪酸代谢对心脏、骨骼肌和肝脏中葡萄糖氧化的长期效应（数小时）也已被发现。这种效应增加了丙酮酸脱氢酶激酶的比活性，进而导致丙酮酸脱氢酶复合物的磷酸化增强及失活。丙酮酸脱氢酶复合物的活性是葡萄糖氧化速率的主要决定因素。脂肪酸对葡萄糖代谢的这一及其他方面的长期效应似乎可能在人类糖尿病胰岛素抵抗的发展中起重要作用。
