Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, Lausanne. Switzerland.
Curr Pharm Des. 2010 May;16(14):1595-608. doi: 10.2174/138161210791164153.
Endocrine beta cells produce and release insulin in order to tightly regulate glucose homeostasis and prevent metabolic pathologies such as Diabetes Mellitus. Optical imaging has contributed greatly to our current understanding of beta cell structure and function. In vitro microscopy of beta cell lines has revealed the localization of molecular components in the cell and more recently their dynamic behavior. In cultured islets, interactions of beta cells with other islet cells and the matrix as well as paracrine and autocrine signaling or reaction to nutrients have been studied. Lastly, microscopy has been performed on tissue sections, visualizing the islets in an environment closer to their natural surroundings. In most efforts to date, the samples have been isolated for investigation and hence have by definition been divorced from their natural environments and deprived of vascularization and innervations. In such a setting the beta cells lack the metabolic information that is primordial to their basic function of maintaining glucose homeostasis. We review optical microscopy; its general principles, its impact in decoding beta cell function and its recent developments towards the more physiologically relevant assessment of beta cell function within the environment of the whole organism. This requires both large imaging depth and fast acquisition times. Only few methods can achieve an adequate compromise. We present extended focus Optical Coherence Microscopy (xfOCM) as a valuable alternative to both confocal microscopy and two photon microscopy (2PM), and discuss its potential in interpreting the mechanisms underlying glucose homeostasis and monitoring impaired islet function.
胰岛β细胞产生并分泌胰岛素,以严格调节葡萄糖稳态,预防糖尿病等代谢性疾病。光学成像是我们目前了解β细胞结构和功能的重要手段。体外β细胞系显微镜观察揭示了细胞内分子成分的定位,以及最近它们的动态行为。在培养的胰岛中,研究了β细胞与其他胰岛细胞和基质之间的相互作用,以及旁分泌和自分泌信号或对营养物质的反应。最后,在组织切片上进行了显微镜检查,在更接近其自然环境的环境中观察胰岛。迄今为止,在大多数研究中,样本都被分离出来进行研究,因此从定义上讲,它们已经脱离了其自然环境,并且失去了血管化和神经支配。在这种情况下,β细胞缺乏维持葡萄糖稳态的基本功能所需的代谢信息。我们回顾了光学显微镜的一般原理及其在解码β细胞功能方面的作用,以及最近在更接近整个生物体环境的情况下对β细胞功能进行更生理相关评估方面的发展。这需要大的成像深度和快速的采集时间。只有少数方法可以达到适当的折衷。我们将扩展焦深光学相干显微镜(xfOCM)作为共聚焦显微镜和双光子显微镜(2PM)的一种有价值的替代方法,并讨论其在解释葡萄糖稳态的机制和监测受损胰岛功能方面的潜力。