Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
Australian Regenerative Medicine Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Diabetes. 2024 Oct 1;73(10):1566-1582. doi: 10.2337/db23-1022.
The islets of Langerhans reside within the endocrine pancreas as highly vascularized microorgans that are responsible for the secretion of key hormones, such as insulin and glucagon. Islet function relies on a range of dynamic molecular processes that include Ca2+ waves, hormone pulses, and complex interactions between islet cell types. Dysfunction of these processes results in poor maintenance of blood glucose homeostasis and is a hallmark of diabetes. Recently, the development of optogenetic methods that rely on light-sensitive molecular actuators has allowed perturbation of islet function with near physiological spatiotemporal acuity. These actuators harness natural photoreceptor proteins and their engineered variants to manipulate mouse and human cells that are not normally light-responsive. Until recently, optogenetics in islet biology has primarily focused on controlling hormone production and secretion; however, studies on further aspects of islet function, including paracrine regulation between islet cell types and dynamics within intracellular signaling pathways, are emerging. Here, we discuss the applicability of optogenetics to islets cells and comprehensively review seminal as well as recent work on optogenetic actuators and their effects in islet function and diabetes mellitus.
胰岛位于内分泌胰腺中,是高度血管化的微型器官,负责分泌关键激素,如胰岛素和胰高血糖素。胰岛功能依赖于一系列动态的分子过程,包括 Ca2+波、激素脉冲以及胰岛细胞类型之间的复杂相互作用。这些过程的功能障碍导致血糖稳态维持不良,是糖尿病的标志。最近,依赖光敏感分子执行器的光遗传学方法的发展允许以接近生理时空精度来干扰胰岛功能。这些执行器利用天然光受体蛋白及其工程变体来操纵通常对光无反应的小鼠和人类细胞。直到最近,胰岛生物学中的光遗传学主要集中在控制激素的产生和分泌上;然而,关于胰岛功能的其他方面的研究,包括胰岛细胞类型之间的旁分泌调节和细胞内信号通路内的动态,正在出现。在这里,我们讨论了光遗传学在胰岛细胞中的适用性,并全面回顾了光遗传学执行器及其在胰岛功能和糖尿病中的作用的开创性和最新工作。