Garvan Institute of Medical Research, Sydney, Australia.
Islets. 2010 Mar-Apr;2(2):127-9. doi: 10.4161/isl.2.2.11240.
Insulin secretion from pancreatic β-cells is triggered by signals arising from the metabolism of glucose and acting through separate initiation and amplification pathways. Despite decades of investigation, crucial details of this mechanism remain poorly understood, especially those relating to the amplifying pathway(s). Advances in this area are vital if we are to understand why insulin secretion fails in type 2 diabetes and to develop strategies to overcome this failure. Indeed, targeting the amplifying pathway(s) would constitute an attractive therapy for augmenting insulin secretion because it would closely link secretory responsiveness to the prevailing glycaemia. It is therefore noteworthy that the possibility of augmenting the amplification pathway(s) has recently been highlighted by studies investigating a metabolic cycle that links the breakdown of triacylglycerol (TAG), release of fatty acid (FA), and subsequent re-incorporation of that FA into TAG. This work reinvigorates and extends the long-standing idea that partitioning of endogenous lipid metabolism towards esterification products promotes the amplification phase of the secretory response. These conceptual advances, and their possible therapeutic application, will be discussed in the following article.
胰腺β细胞的胰岛素分泌是由葡萄糖代谢产生的信号触发的，这些信号通过独立的起始和放大途径发挥作用。尽管经过了几十年的研究，但该机制的关键细节仍未得到很好的理解，尤其是与放大途径相关的细节。如果我们要了解为什么 2 型糖尿病中胰岛素分泌会失败，并制定克服这种失败的策略，那么在这一领域取得进展至关重要。事实上，针对放大途径将是一种增强胰岛素分泌的有吸引力的治疗方法，因为它将使分泌反应与当前的血糖密切相关。因此，值得注意的是，最近的研究强调了增强放大途径的可能性，这些研究调查了一个代谢循环，该循环将三酰甘油 (TAG) 的分解、脂肪酸 (FA) 的释放以及随后将该 FA 重新掺入 TAG 联系起来。这项工作重振并扩展了长期以来的观点，即将内源性脂质代谢向酯化产物的分配促进了分泌反应的放大阶段。本文将讨论这些概念上的进展及其可能的治疗应用。
