Significant advances have been made in deciphering the mechanisms underlying fuel-stimulated insulin secretion by pancreatic beta cells. The contribution of the triggering/ATP-sensitive potassium (KATP)-dependent Ca2+ signalling and KATP-independent amplification pathways, that include anaplerosis and lipid signalling of glucose-stimulated insulin secretion (GSIS), are well established. A proposed model included a key role for a metabolic partitioning 'switch', the acetyl-CoA carboxylase (ACC)/malonyl-CoA/carnitine palmitoyltransferase-1 (CPT-1) axis, in beta cell glucose and fatty acid signalling for insulin secretion. This model has gained overwhelming support from a number of studies in recent years and is now refined through its link to the glycerolipid/NEFA cycle that provides lipid signals through its lipolysis arm. Furthermore, acetyl-CoA carboxylase may also control beta cell growth. Here we review the evidence supporting a role for the ACC/malonyl-CoA/CPT-1 axis in the control of GSIS and its particular importance under conditions of elevated fatty acids (e.g. fasting, excess nutrients, hyperlipidaemia and diabetes). We also document how it is linked to a more global lipid signalling system that includes the glycerolipid/NEFA cycle.

中文翻译：

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胰腺β细胞功能中与脂质相​​关的代谢信号网络。

在破译胰岛β细胞燃料刺激胰岛素分泌的机制方面已取得重大进展。触发/ ATP敏感性钾（KATP）依赖性Ca2 +信号传导和KATP非依赖性扩增途径（包括葡萄糖刺激的胰岛素分泌（GSIS）的动脉粥样硬化和脂质信号传导）的贡献已得到公认。拟议中的模型包括代谢分区“开关”的关键作用，即乙酰辅酶A羧化酶（ACC）/丙二酰辅酶A /肉碱棕榈酰转移酶-1（CPT-1）轴在β细胞葡萄糖和脂肪酸信号传导中的胰岛素分泌。近年来，该模型获得了许多研究的压倒性支持，现在通过与通过脂解臂提供脂质信号的甘油脂/ NEFA循环的联系进行了完善。此外，乙酰辅酶A羧化酶也可以控制β细胞的生长。在这里，我们回顾了支持ACC /丙二酰辅酶A / CPT-1轴在GSIS控制中的作用的证据，以及在脂肪酸升高（例如禁食，营养过多，高脂血症和糖尿病）的情况下其重要性的证据。我们还记录了它如何与包括甘油脂/ NEFA循环在内的更全面的脂质信号系统连接。