Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Diabet Med. 2023 Dec;40(12):e15198. doi: 10.1111/dme.15198. Epub 2023 Sep 2.
Type 2 diabetes (T2D) in humans is typically preceded by elevated levels of circulatory long-chain free fatty acids (LC-FFA). These excess LC-FFA are widely thought to be taken up by pancreatic β-cells, contributing to their dysfunction and death during the development of T2D; a process that has been termed lipotoxicity. Depending on their degree of saturation and carbon chain length, LC-FFA can exert different effects on pancreatic β-cells viability and function in vitro. Long-chain saturated fatty acids (LC-SFA) are thought to be toxic, whereas monounsaturated fatty acids are not and may even offer protection against the toxic effects of LC-SFAs. However, the mechanism of LC-FFA uptake into pancreatic β-cells is poorly understood, partly because it has been an understudied area of research. Determining how LC-FFA are taken up into β-cells is crucial for later formulation of therapies to prevent potential cellular overload of LC-FFA, thereby slowing the onset of T2D. In this work, we detail more than 40 years of literature investigating the role of membrane-associated transport proteins in LC-FFA uptake. By focussing on what is known in other cell types, we highlight where we can extrapolate our current understanding of protein-mediated transport to β-cells and uncover where further understanding is required.
2 型糖尿病（T2D）患者的循环长链游离脂肪酸（LC-FFA）水平通常升高。这些过量的 LC-FFA 被广泛认为被胰腺β细胞摄取，导致它们在 T2D 发展过程中功能障碍和死亡；这一过程被称为脂毒性。根据其饱和度和碳链长度的不同，LC-FFA 可以在体外对胰腺β细胞的存活和功能产生不同的影响。长链饱和脂肪酸（LC-SFA）被认为是有毒的，而单不饱和脂肪酸则不是，甚至可能对 LC-SFA 的毒性作用提供保护。然而，LC-FFA 进入胰腺β细胞的机制还知之甚少，部分原因是它一直是一个研究不足的领域。确定 LC-FFA 如何进入β细胞对于以后制定预防 LC-FFA 潜在细胞过载的治疗方法至关重要，从而减缓 T2D 的发病。在这项工作中，我们详细介绍了 40 多年来研究膜相关转运蛋白在 LC-FFA 摄取中的作用的文献。通过关注其他细胞类型中已知的内容，我们强调了可以将我们对蛋白介导运输的现有理解外推到β细胞的地方，并揭示了需要进一步理解的地方。
