Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
Diabetologia. 2024 Dec;67(12):2626-2636. doi: 10.1007/s00125-024-06253-x. Epub 2024 Aug 24.
The tight regulation of glucose and lipid metabolism is crucial for maintaining metabolic health. Dysregulation of these processes can lead to the development of metabolic diseases. Secreted factors, or hormones, play an essential role in the regulation of glucose and lipid metabolism, thus also playing an important role in the development of metabolic diseases such as type 2 diabetes and obesity. Given the important roles of secreted factors, there has been significant interest in identifying new secreted factors and new functions for existing secreted factors that control glucose and lipid metabolism. In this review, we evaluate novel secreted factors or novel functions of existing factors that regulate glucose and lipid metabolism discovered in the last decade, including secreted isoform of endoplasmic reticulum membrane complex subunit 10, vimentin, cartilage intermediate layer protein 2, isthmin-1, lipocalin-2, neuregulin-1 and neuregulin-4. We discuss their discovery, tissues of origin, mechanisms of action and sex differences, emphasising their potential to regulate metabolic processes central to diabetes. Additionally, we discuss the translational barriers, particularly the absence of identified receptors, that hamper their functional characterisation and further therapeutic development. Ultimately, the identification of new secreted factors may give insights into previously unidentified pathways of disease progression and mechanisms of glucose and lipid homeostasis.
葡萄糖和脂质代谢的严格调节对维持代谢健康至关重要。这些过程的失调可导致代谢疾病的发生。分泌因子或激素在葡萄糖和脂质代谢的调节中发挥着重要作用，因此在代谢疾病（如 2 型糖尿病和肥胖症）的发生中也起着重要作用。鉴于分泌因子的重要作用，人们对鉴定控制葡萄糖和脂质代谢的新分泌因子和现有分泌因子的新功能产生了浓厚的兴趣。在这篇综述中，我们评估了过去十年中发现的调节葡萄糖和脂质代谢的新分泌因子或现有因子的新功能，包括内质网膜复合物亚基 10 的分泌异构体、波形蛋白、软骨中层蛋白 2、胰岛素原-1、脂联素-2、神经调节素-1 和神经调节素-4。我们讨论了它们的发现、起源组织、作用机制和性别差异，强调了它们调节与糖尿病密切相关的代谢过程的潜力。此外，我们还讨论了转化障碍，特别是缺乏已鉴定的受体，这阻碍了它们的功能特征和进一步的治疗开发。最终，新分泌因子的鉴定可能会深入了解以前未知的疾病进展途径和葡萄糖及脂质稳态的机制。
