Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warszawa, Poland.
Rudolf-Virchow-Zentrum. Center for Integrative and Translational Bioimaging, University of Würzburg, 97080, Würzburg, Germany.
Biochem Biophys Res Commun. 2024 Nov 19;734:150753. doi: 10.1016/j.bbrc.2024.150753. Epub 2024 Sep 26.
Platelets, originally described for their role in blood coagulation, are now also recognized as key players in modulating inflammation, tissue regeneration, angiogenesis, and carcinogenesis. Recent evidence suggests that platelets also influence insulin secretion from pancreatic β cells. The multifaceted functions of platelets are mediated by the factors stored in their alpha granules (AGs) and dense granules (DGs). AGs primarily contain proteins, while DGs are rich in small molecules, and both types of granules are released during blood coagulation. Specific components stored in AGs and DGs are implicated in various inflammatory, regenerative, and tumorigenic processes. However, the relative contributions of AGs and DGs to the regulation of pancreatic β cell function have not been previously explored.
In this study, we utilized mouse models deficient in AG content (neurobeachin-like 2 (Nbeal2) -deficient mice) and models with defective DG release (Unc13d-deficiency in bone marrow-derived cells) to investigate the impact of platelet granules on insulin secretion from pancreatic β cells.
Our findings indicate that AG deficiency has little to no effect on pancreatic β cell function and glucose homeostasis. Conversely, mice with defective DG release exhibited glucose intolerance and reduced insulin secretion. Furthermore, Unc13d-deficiency in hematopoietic stem cells led to a reduction in adipose tissue gain in obese mice.
Obtained data suggest that DGs, but not AGs, mediate the influence of platelets on pancreatic β cells, thereby modulating glucose metabolism.
血小板最初因其在血液凝固中的作用而被描述，现在也被认为是调节炎症、组织再生、血管生成和癌变的关键因素。最近的证据表明，血小板还影响胰腺β细胞的胰岛素分泌。血小板的多方面功能是由其α颗粒（AGs）和致密颗粒（DG）中储存的因子介导的。AGs 主要包含蛋白质，而 DG 富含小分子，这两种类型的颗粒在血液凝固过程中释放。储存在 AGs 和 DG 中的特定成分与各种炎症、再生和致瘤过程有关。然而，AGs 和 DGs 对胰腺β细胞功能调节的相对贡献以前尚未被探索过。
在这项研究中，我们利用缺乏 AG 含量的小鼠模型（神经海滩蛋白样 2（Nbeal2）缺陷小鼠）和 DG 释放缺陷模型（骨髓来源细胞中 Unc13d 缺陷）来研究血小板颗粒对胰腺β细胞胰岛素分泌的影响。
我们的研究结果表明，AG 缺乏对胰腺β细胞功能和葡萄糖稳态几乎没有影响。相反，DG 释放缺陷的小鼠表现出葡萄糖不耐受和胰岛素分泌减少。此外，造血干细胞中 Unc13d 的缺陷导致肥胖小鼠脂肪组织获得减少。
获得的数据表明，DG 而不是 AGs 介导血小板对胰腺β细胞的影响，从而调节葡萄糖代谢。
