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Optogenetics in pancreatic islets: Actuators and effects
Diabetes ( IF 6.2 ) Pub Date : 2024-07-08 , DOI: 10.2337/db23-1022
Christina G Gangemi 1, 2, 3 , Harald Janovjak 1
Affiliation  

The Islets of Langerhans reside within the endocrine pancreas as highly vascularised micro-organs 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 calcium (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. Very recently, the development of optogenetic methods that rely on light-sensitive molecular actuators has allowed perturbing islet function with near physiological spatio-temporal 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 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 (DM).

中文翻译:


胰岛的光遗传学:驱动器和效应



朗格汉斯岛位于内分泌胰腺内,是高度血管化的微器官,负责分泌胰岛素和胰高血糖素等关键激素。胰岛功能依赖于一系列动态分子过程,包括钙 (Ca2+) 波、激素脉冲以及胰岛细​​胞类型之间复杂的相互作用。这些过程的功能障碍导致血糖稳态维持不良,是糖尿病的一个标志。最近,依赖光敏分子致动器的光遗传学方法的发展使得以接近生理时空敏锐度扰动胰岛功能成为可能。这些执行器利用天然光感受器蛋白及其工程变体来操纵通常不响应光的小鼠和人类细胞。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正在兴起,包括胰岛细胞类型之间的旁分泌调节和细胞内信号通路的动态。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致动器及其对胰岛功能和糖尿病(DM)影响的开创性和最新研究。
更新日期:2024-07-08
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