Corkey B E, Glennon M C, Chen K S, Deeney J T, Matschinsky F M, Prentki M
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
J Biol Chem. 1989 Dec 25;264(36):21608-12.
To gain insight into the relationship between acyl coenzyme A (CoA) esters and glucose-induced insulin release, acyl-CoA profiles were determined in clonal pancreatic beta-cells (HIT). A high sensitivity high performance liquid chromatography method was used to measure malonyl, succinyl, beta-hydroxy beta-methylglutaryl and acetyl-CoA esters and free CoASH. Malonyl-CoA content increased more than 3-fold following exposure of HIT cells to 10 mM glucose. The rise in malonyl-CoA, which preceded insulin secretion, was evident 2 min after exposure to glucose and was sustained for at least 30 min. The increase in malonyl-CoA was associated with inhibition of fatty acid oxidation, increased de novo lipid synthesis and a rise in diacylglycerol content. Succinyl-CoA levels, which may reflect anaplerotic influx into the citric acid cycle, were elevated in the presence of glucose. The concentration of acetyl-CoA and the ratio of free CoASH to acetyl-CoA was unchanged. The data are consistent with a metabolic model in which malonyl-CoA mediates the switch from fatty acid catabolism to lipid synthesis during glucose stimulation of beta-cells. We suggest that these changes in lipid metabolism, by leading to increased diacylglycerol synthesis or protein acylation could play a pivotal role in the regulation of the sustained phase of insulin secretion.
为深入了解酰基辅酶A（CoA）酯与葡萄糖诱导的胰岛素释放之间的关系，我们测定了克隆胰腺β细胞（HIT）中的酰基辅酶A谱。采用高灵敏度高效液相色谱法测量丙二酰、琥珀酰、β-羟基-β-甲基戊二酰和乙酰辅酶A酯以及游离辅酶A（CoASH）。将HIT细胞暴露于10 mM葡萄糖后，丙二酰辅酶A含量增加了3倍多。丙二酰辅酶A的升高先于胰岛素分泌，在暴露于葡萄糖2分钟后即可明显观察到，并持续至少30分钟。丙二酰辅酶A的增加与脂肪酸氧化的抑制、从头脂质合成的增加以及二酰甘油含量的升高有关。琥珀酰辅酶A水平在葡萄糖存在下升高，这可能反映了回补途径进入柠檬酸循环的情况。乙酰辅酶A的浓度以及游离CoASH与乙酰辅酶A的比率没有变化。这些数据与一个代谢模型一致，即在β细胞受到葡萄糖刺激时，丙二酰辅酶A介导了从脂肪酸分解代谢向脂质合成的转变。我们认为，脂质代谢的这些变化，通过导致二酰甘油合成增加或蛋白质酰化，可能在胰岛素分泌持续阶段的调节中起关键作用。
