Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years.
Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years.
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DOI：
10.1002/(sici)1099-0895(199812)14:4
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发表时间：
1998-12
期刊：
影响因子：
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通讯作者：
P. J. Randle
中科院分区：
文献类型：
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作者：
P. J. Randle
动物组织中底物之间的呼吸竞争至少已有80年的历史。最重要的相互作用，定量是在葡萄糖和脂肪酸之间。1963年，葡萄糖脂肪酸循环的起点是认识到葡萄糖和脂肪酸之间的代谢关系是相互的，而不是依赖的。葡萄糖供应促进葡萄糖氧化以及葡萄糖和脂质储存，并抑制脂肪酸氧化。提供游离脂肪酸促进脂肪酸氧化和储存，抑制葡萄糖氧化，如果糖原储备不完全，则可能促进葡萄糖储存。这篇综述主要关注人体内的证据。作者认为，脂肪酸对全身葡萄糖利用和氧化（主要是肌肉）的抑制作用的证据是决定性的，并且介导这些作用的酶机制已得到充分确立。还有很多证据表明，脂肪酸氧化抑制葡萄糖氧化并刺激肝脏中葡萄糖形成，并且酶机制也是已知的。脂肪酸在胰岛β细胞胰岛素分泌反应中的容许作用现已确立，并可视为保护持续提供呼吸底物的机制。胰岛β细胞长期暴露于脂肪酸会损害胰岛素对葡萄糖的分泌反应，其机制是已知的。有令人信服的证据表明，脂肪酸氧化可能会损害不受控制的1型和2型糖尿病中的葡萄糖氧化，但没有令人信服的证据表明脂肪酸在2型糖尿病中减少葡萄糖储存（糖原沉积）中发挥作用。在人和实验动物中，可能在血浆FFA长期升高后出现的葡萄糖储存抑制与糖原补充相关，而2型糖尿病中葡萄糖储存抑制与糖原耗竭相关。脂肪酸在2型糖尿病碳水化合物代谢紊乱中的确切作用是一个可以自信地预测未来进展的领域。
Competition for respiration between substrates in animal tissues has been known for at least 80 years. The most important interaction, quantitatively is between glucose and fatty acids. The starting point in 1963 for the so called Glucose Fatty Acid Cycle was the realisation that the metabolic relationship between glucose and fatty acids is reciprocal and not dependent. Glucose provision promotes glucose oxidation and glucose and lipid storage, and inhibits fatty acid oxidation. Provision of free fatty acids promotes fatty acid oxidation and storage, inhibits glucose oxidation and may promote glucose storage if glycogen reserves are incomplete. This review is concerned predominantly with evidence in man in vivo. In the authors opinion the evidence for inhibitory effects of fatty acids on whole body glucose utilization ad oxidation (predominantly muscles) is decisive and enzyme mechanisms mediating these effects are well established. There is also much evidence that fatty acid oxidation inhibits glucose oxidation and stimulates glucose formation in liver and again enzyme mechanism are known. A permissive role for fatty acids in the insulin secretory response of islet beta-cells has now been firmly established and can be visualised as a mechanism to protect continuing provision of respiratory substrate. Longer term exposure of islet beta-cells to fatty acids impairs the insulin secretory response to glucose and mechanisms are known. There is compelling evidence that fatty acid oxidation may impair glucose oxidation in uncontrolled Type 1 and Type 2 diabetes, but no convincing evidence that fatty acids have a role in diminished glucose storage (glycogen deposition) in Type 2 diabetes. The inhibition of glucose storage which may follow prolonged elevation of plasma FFA in man and experimental animals is associated with glycogen repletion whereas the inhibition of glucose storage in Type 2 diabetes is associated with glycogen depletion. The precise role of fatty acids in disturbed carbohydrate metabolism in Type 2 diabetes is an area where future progress is confidently predicted.