Children's Health Research Institute, University of Western Ontario, London, ON N6C 2V5, Canada.
Department of Physiology & Pharmacology, University of Western Ontario, London, ON N6C 2V5, Canada.
Endocrinology. 2022 Nov 14;164(1). doi: 10.1210/endocr/bqac179.
Shortcomings in cell-based therapies for patients with diabetes have been revealed to be, in part, a result of an improper extracellular matrix (ECM) environment. In vivo, pancreatic islets are emersed in a diverse ECM that provides physical support and is crucial for healthy function. β1-Integrin receptors have been determined to be responsible for modulation of beneficial interactions with ECM proteins influencing beta-cell development, proliferation, maturation, and function. β1-Integrin signaling has been demonstrated to augment insulin secretion by impacting the actin cytoskeleton via activation of focal adhesion kinase and downstream signaling pathways. In other secretory cells, evidence of a bidirectional relationship between integrins and exocytotic machinery has been demonstrated, and, thus, this relationship could be present in pancreatic beta cells. In this review, we will discuss the role of ECM-β1-integrin interplay with exocytotic proteins in controlling pancreatic beta-cell insulin secretion through their dynamic and unique signaling pathway.
细胞疗法在治疗糖尿病患者方面的不足部分原因是细胞外基质（ECM）环境不当。在体内，胰岛沉浸在多样化的 ECM 中，该 ECM 为胰岛提供物理支撑，对其健康功能至关重要。β1-整合素受体负责调节与 ECM 蛋白的有益相互作用，从而影响β细胞的发育、增殖、成熟和功能。β1-整合素信号通过激活粘着斑激酶和下游信号通路影响肌动蛋白细胞骨架，从而增强胰岛素分泌。在其他分泌细胞中，已经证明整合素和胞吐机制之间存在双向关系，因此，这种关系可能存在于胰腺β细胞中。在这篇综述中，我们将讨论 ECM-β1-整合素相互作用与胞吐蛋白在通过其动态和独特的信号通路控制胰腺β细胞胰岛素分泌中的作用。
